Potential clinical utility of multiple system atrophy biomarkers

References

• Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015;372:249–263.
   PubMed Web of Science ®Google Scholar
• Graham JG, Oppenheimer DR. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1969;32:28–34.
   PubMed Web of Science ®Google Scholar
• Spillantini MG, Gedert M. Synucleinopathies: past, present and future. Neuropathol Appl Neurobiol. 2016;42:3–5.
   PubMed Web of Science ®Google Scholar
• Goedert M, Jakes R, Spillantini MG. The synucleinopathies: twenty years on. J Parkinsons Dis. 2017;7:S53–S71.
   PubMedGoogle Scholar
• Koga S, Dickson DW. Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy. J Neurol Neurosurg Psychiatry. 2017.
   PubMedGoogle Scholar
• Jellinger KA. Multiple system atrophy: an oligodendroglioneural synucleinopathy in print. J Alzheimer’s Dis. 2017. DOI:10.3233/JAD-170397.
   PubMedGoogle Scholar
• Jellinger KA, Lantos PL. Papp-Lantos inclusions and the pathogenesis of multiple system atrophy: an update. Acta Neuropathol. 2010;119:657–667.
   PubMed Web of Science ®Google Scholar
• Trojanowski JQ, Revesz T. Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy. Neuropathol Appl Neurobiol. 2007;33:615–620.
   PubMed Web of Science ®Google Scholar
• Jellinger KA, Wenning GK. Multiple system atrophy: pathogenic mechanisms and biomarkers. J Neural Transm (Vienna). 2016;123:555–572.
   PubMed Web of Science ®Google Scholar
• Ahmed Z, Asi YT, Sailer A, et al. The neuropathology, pathophysiology and genetics of multiple system atrophy. Neuropathol Appl Neurobiol. 2012;38:4–24.
   PubMed Web of Science ®Google Scholar
• Cykowski MD, Coon EA, Powell SZ, et al. Expanding the spectrum of neuronal pathology in multiple system atrophy. Brain. 2015;138:2293–2309.
   PubMed Web of Science ®Google Scholar
• Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–676.
   PubMed Web of Science ®Google Scholar
• Lyoo CH, Jeong Y, Ryu YH, et al. Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy. Brain. 2008;131:438–446.
   PubMed Web of Science ®Google Scholar
• Wenning GK, Geser F, Krismer F, et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol. 2013;12:264–274.
   PubMed Web of Science ®Google Scholar
• Yabe I, Soma H, Takei A, et al. MSA-C is the predominant clinical phenotype of MSA in Japan: analysis of 142 patients with probable MSA. J Neurol Sci. 2006;249:115–121.
   PubMed Web of Science ®Google Scholar
• Watanabe H, Saito Y, Terao S, et al. Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain. 2002;125:1070–1083.
   PubMed Web of Science ®Google Scholar
• Ozawa T, Onodera O. Multiple system atrophy: clinicopathological characteristics in Japanese patients. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93:251–258.
   PubMed Web of Science ®Google Scholar
• Bower JH, Maraganore DM, McDonnell SK, et al. Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology. 1997;49:1284–1288.
   PubMed Web of Science ®Google Scholar
• Quinn N. Multiple system atrophy–the nature of the beast. J Neurol Neurosurg Psychiatry. 1989;Suppl:78–89.
   PubMedGoogle Scholar
• Jecmenica-Lukic M, Poewe W, Tolosa E, et al. Premotor signs and symptoms of multiple system atrophy. Lancet Neurol. 2012;11:361–368.
   PubMed Web of Science ®Google Scholar
• Xie T, Kang UJ, Kuo S-H, et al. Comparison of clinical features in pathologically confirmed PSP and MSA patients followed at a tertiary center. Npj Parkinson’s Dis. 2015;1:15007.
   PubMed Web of Science ®Google Scholar
• Brown RC, Lockwood AH, Sonawane BR. Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspect. 2005;113:1250–1256.
   PubMed Web of Science ®Google Scholar
• Fujioka S, Ogaki K, Tacik PM, et al. Update on novel familial forms of Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord. 2014;20(Suppl 1):S29–34.
   PubMedGoogle Scholar
• Vidal JS, Vidailhet M, Derkinderen P, et al. Familial aggregation in atypical Parkinson’s disease: a case control study in multiple system atrophy and progressive supranuclear palsy. J Neurol. 2010;257:1388–1393.
   PubMed Web of Science ®Google Scholar
• Wenning GK, Stefanova N. Recent developments in multiple system atrophy. J Neurol. 2009;256:1791–1808.
   PubMed Web of Science ®Google Scholar
• Ozawa T. Pathology and genetics of multiple system atrophy: an approach to determining genetic susceptibility spectrum. Acta Neuropathol. 2006;112:531–538.
   PubMed Web of Science ®Google Scholar
• Federoff M, Schottlaender LV, Houlden H, et al. Multiple system atrophy: the application of genetics in understanding etiology. Clin Auton Res. 2015;25:19–36.
   PubMed Web of Science ®Google Scholar
• Sailer A, Scholz SW, Nalls MA, et al. A genome-wide association study in multiple system atrophy. Neurology. 2016;87:1591–1598.
   PubMed Web of Science ®Google Scholar
• Nussbaum RL. Genetics of synucleinopathies. Cold Spring Harb Perspect Med; 2017 Feb 17, doi 10.1101/cshperspect.a024109.
   Google Scholar
• Dehay B, Vila M, Bezard E, et al. Alpha-synuclein propagation: new insights from animal models. Mov Disord. 2016;31:161–168.
   PubMed Web of Science ®Google Scholar
• McCann H, Cartwright H, Halliday GM. Neuropathology of alpha-synuclein propagation and Braak hypothesis. Mov Disord. 2016;31:152–160.
   PubMed Web of Science ®Google Scholar
• Woerman AL, Watts JC, Aoyagi A, et al. alpha-Synuclein: multiple system atrophy prions. Cold Spring Harb Perspect Med. 2017. in print. DOI:10.1101/cshperspect.a024588.
   PubMedGoogle Scholar
• Goedert M, Masuda-Suzukake M, Falcon B. Like prions: the propagation of aggregated tau and alpha-synuclein in neurodegeneration. Brain. 2017;140:266–278.
   PubMed Web of Science ®Google Scholar
• Rohan Z, Milenkovic I, Lutz MI, et al. Shared and distinct patterns of oligodendroglial response in alpha-synucleinopathies and tauopathies. J Neuropathol Exp Neurol. 2016;75:1100–1109.
   PubMed Web of Science ®Google Scholar
• Jellinger KA. Multiple system atrophy - a synucleinopathy with specific glioneuronal degeneration. Austin J Clin Neurol. 2015;2:1071.
   Google Scholar
• Jellinger KA. What’s new in multiple system atrophy. Curr Neurobio. 2015;6:11–14.
   Google Scholar
• Bleasel JM, Halliday GM, Kim WS. Animal modeling an oligodendrogliopathy - multiple system atrophy. Acta Neuropathol Commun. 2016;4:12.
   PubMed Web of Science ®Google Scholar
• Wenning GK, Stefanova N, Jellinger KA, et al. Multiple system atrophy: a primary oligodendrogliopathy. Ann Neurol. 2008;64:239–246.
   PubMed Web of Science ®Google Scholar
• Halliday GM. Re-evaluating the glio-centric view of multiple system atrophy by highlighting the neuronal involvement. Brain. 2015;138:2116–2119.
   PubMed Web of Science ®Google Scholar
• Burn DJ, Jaros E. Multiple system atrophy: cellular and molecular pathology. Mol Pathol. 2001;54:419–426.
   PubMedGoogle Scholar
• Asi YT, Simpson JE, Heath PR, et al. Alpha-synuclein mRNA expression in oligodendrocytes in MSA. Glia. 2014;62:964–970.
   PubMed Web of Science ®Google Scholar
• Reyes JF, Rey NL, Bousset L, et al. Alpha-synuclein transfers from neurons to oligodendrocytes. Glia. 2014;62:387–398.
   PubMed Web of Science ®Google Scholar
• Rey NL, George S, Brundin P, et al. the word: precise animal models and validated methods are vital when evaluating prion-like behaviour of alpha-synuclein. Neuropathol Appl Neurobiol. 2016;42:51–76.
   PubMed Web of Science ®Google Scholar
• Ubhi K, Rockenstein E, Mante M, et al. Neurodegeneration in a transgenic mouse model of multiple system atrophy is associated with altered expression of oligodendroglial-derived neurotrophic factors. J Neurosci. 2010;30:6236–6246.
   PubMed Web of Science ®Google Scholar
• Goedert M. Alzheimer’s and Parkinson’s diseases: the prion concept in relation to assembled Abeta, tau, and alpha-synuclein. Science. 2015;349:1255555.
   PubMed Web of Science ®Google Scholar
• Brettschneider J, Del Tredici K, Lee VM, et al. Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci. 2015;16:109–120.
   PubMed Web of Science ®Google Scholar
• Prusiner SB, Woerman AL, Mordes DA, et al. Evidence for alpha-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci USA. 2015;112:E5308–17.
   PubMed Web of Science ®Google Scholar
• Peelaerts W, Bousset L, Van Der Perren A, et al. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature. 2015;522:340–344.
   PubMed Web of Science ®Google Scholar
• Melki R. Role of different alpha-synuclein strains in synucleinopathies, similarities with other neurodegenerative diseases. J Parkinsons Dis. 2015;5:217–227.
   PubMedGoogle Scholar
• Peelaerts W, Baekelandt V. α-Synuclein strains and the variable pathologies of synucleinopathies. J Neurochem. 2016;139, Suppl 1:256–274.
   PubMed Web of Science ®Google Scholar
• Walsh DM, Selkoe DJ. A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration. Nat Rev Neurosci. 2016;17:251–260.
   PubMed Web of Science ®Google Scholar
• Bendor JT, Logan TP, Edwards RH. The function of alpha-synuclein. Neuron. 2013;79:1044–1066.
   PubMed Web of Science ®Google Scholar
• Guo JL, Lee VM. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med. 2014;20:130–138.
   PubMed Web of Science ®Google Scholar
• Desplats P, Lee HJ, Bae EJ, et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A. 2009;106:13010–13015.
   PubMed Web of Science ®Google Scholar
• Luk KC, Kehm V, Carroll J, et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338:949–953.
   PubMed Web of Science ®Google Scholar
• Luk KC, Kehm VM, Zhang B, et al. Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice. J Exp Med. 2012;209:975–986.
   PubMed Web of Science ®Google Scholar
• Valdinocci D, Radford RA, Siow SM, et al. Potential modes of intercellular alpha-synuclein transmission. Int J Mol Sci. 2017;18:469.
   Web of Science ®Google Scholar
• Shimozawa A, Ono M, Takahara D, et al. Propagation of pathological alpha-synuclein in marmoset brain. Acta Neuropathol Commun. 2017;5:12.
   PubMed Web of Science ®Google Scholar
• Tofaris GK, Goedert M, Spillantini MG. The transcellular propagation and intracellular trafficking of alpha-synuclein. Cold Spring Harb Perspect Med. 2016. in print. DOI:10.1101/cshperspect.a024380.
   Web of Science ®Google Scholar
• Hasegawa M, Nonaka T, Masuda-Suzukake M. alpha-Synuclein: experimental pathology. Cold Spring Harb Perspect Med. 2016;6. DOI:10.1101/cshperspect.a024273
   PubMed Web of Science ®Google Scholar
• Bassil F, Guerin PA, Dutheil N, et al. Viral-mediated oligodendroglial alpha-synuclein expression models multiple system atrophy. Mov Disord. 2017;32:1230-1239.
   PubMed Web of Science ®Google Scholar
• Mandel RJ, Marmion DJ, Kirik D, et al. Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates. Acta Neuropathol Commun. 2017;5:47.
   PubMed Web of Science ®Google Scholar
• Beraud D, Hathaway HA, Trecki J, et al. Microglial activation and antioxidant responses induced by the Parkinson’s disease protein alpha-synuclein. J Neuroimmune Pharmacol. 2013;8:94–117.
   PubMed Web of Science ®Google Scholar
• Ota K, Obayashi M, Ozaki K, et al. Relocation of p25alpha/tubulin polymerization promoting protein from the nucleus to the perinuclear cytoplasm in the oligodendroglia of sporadic and COQ2 mutant multiple system atrophy. Acta Neuropathol Commun. 2014;2:136.
   PubMed Web of Science ®Google Scholar
• Oláh J, Bertrand P, Ovadi J. Role of the microtubule-associated TPPP/p25 in Parkinson’s and related diseases and its therapeutic potential. Expert Rev Proteomics. 2017;14:301–309.
   PubMed Web of Science ®Google Scholar
• Grigoletto J, Pukass K, Gamliel A, et al. Higher levels of myelin phospholipids in brains of neuronal alpha-synuclein transgenic mice precede myelin loss. Acta Neuropathol Commun. 2017;5:37.
   PubMed Web of Science ®Google Scholar
• Don AS, Hsiao JH, Bleasel JM, et al. Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy. Acta Neuropathol Commun. 2014;2:150.
   PubMed Web of Science ®Google Scholar
• Wong JH, Halliday GM, Kim WS. Exploring myelin dysfunction in multiple system atrophy. Exp Neurobiol. 2014;23:337–344.
   PubMedGoogle Scholar
• Ettle B, Schlachetzki JC, Winkler J. Oligodendroglia and myelin in neurodegenerative diseases: more than just bystanders? Mol Neurobiol. 2016;53:3046–3062.
   PubMed Web of Science ®Google Scholar
• Bassil F, Monvoisin A, Canron MH, et al. Region-specific alterations of matrix metalloproteinase activity in multiple system atrophy. Mov Disord. 2015;30:1802–1812.
   PubMed Web of Science ®Google Scholar
• Ubhi K, Rockenstein E, Kragh C, et al. Widespread microRNA dysregulation in multiple system atrophy - disease-related alteration in miR-96. Eur J Neurosci. 2014;39:1026–1041.
   PubMed Web of Science ®Google Scholar
• Bleasel JM, Wong JH, Halliday GM, et al. Lipid dysfunction and pathogenesis of multiple system atrophy. Acta Neuropathol Commun. 2014;2:15.
   PubMed Web of Science ®Google Scholar
• Bi C, Qian H. Cholesterol homeostasis and the pathogenesis of multiple system atrophy. J Alzheimers Dis Parkinsonism. 2017;7:3.
   Google Scholar
• Chen Y, Cao B, Yang J, et al. Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson’s disease and multiple system atrophy in a Chinese population. J Neurol. 2015;262:2478–2483.
   PubMed Web of Science ®Google Scholar
• Soma H, Yabe I, Takei A, et al. Associations between multiple system atrophy and polymorphisms of SLC1A4, SQSTM1, and EIF4EBP1 genes. Mov Disord. 2008;23:1161–1167.
   PubMed Web of Science ®Google Scholar
• Stefanova N, Reindl M, Neumann M, et al. Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov Disord. 2007;22:2196–2203.
   PubMed Web of Science ®Google Scholar
• Fellner L, Stefanova N. The role of glia in alpha-synucleinopathies. Mol Neurobiol. 2013;47:575–586.
   PubMed Web of Science ®Google Scholar
• Miki Y, Tanji K, Mori F, et al. AMBRA1, a novel alpha-synuclein-binding protein, is implicated in the pathogenesis of multiple system atrophy. Brain Pathol. 2017. in print. DOI:10.1111/bpa.12461.
   Google Scholar
• Ubhi K, Lee PH, Adame A, et al. Mitochondrial inhibitor 3-nitroproprionic acid enhances oxidative modification of alpha-synuclein in a transgenic mouse model of multiple system atrophy. J Neurosci Res. 2009;87:2728–2739.
   PubMed Web of Science ®Google Scholar
• Federoff M. Multiple system atrophy: moving towards a multi-mechanistic hypothesis. Int J Neurol Neurother. 2016;3:046.
   Google Scholar
• Krismer F, Wenning GK. Multiple system atrophy: insights into a rare and debilitating movement disorder. Nat Rev Neurol. 2017;13:232–243.
   PubMed Web of Science ®Google Scholar
• Batla A, Stamelou M, Mensikova K, et al. Markedly asymmetric presentation in multiple system atrophy. Parkinsonism Relat Disord. 2013;19:901–905.
   PubMed Web of Science ®Google Scholar
• Kaindlstorfer C, Granata R, Wenning GK. Tremor in multiple system atrophy - a review. Tremor Other Hyperkinet Mov (N Y). 2013;3. DOI:10.7916/D8NV9GZ9.
   PubMedGoogle Scholar
• Köllensperger M, Geser F, Ndayisaba JP, et al. Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry. Mov Disord. 2010;25:2604–2612.
   PubMed Web of Science ®Google Scholar
• Köllensperger M, Geser F, Seppi K, et al. Red flags for multiple system atrophy. Mov Disord. 2008;23:1093–1099.
   PubMed Web of Science ®Google Scholar
• Wenning GK, Ben-Shlomo Y, Hughes A, et al. What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson’s disease? J Neurol Neurosurg Psychiatry. 2000;68:434–440.
   PubMed Web of Science ®Google Scholar
• Eschlböck S, Benke T, Boesch S, et al. Non-motor symptoms and gender differences in multiple system atrophy (abstr.). NeuroLogisch. 2017;Suppl 1:8.
   Google Scholar
• Jimenez-Jimenez FJ, Alonso-Navarro H, Garcia-Martin E, et al. Cerebrospinal fluid biochemical studies in patients with Parkinson’s disease: toward a potential search for biomarkers for this disease. Front Cell Neurosci. 2014;8:369.
   PubMed Web of Science ®Google Scholar
• Colosimo C. Nonmotor presentations of multiple system atrophy. Nat Rev Neurol. 2011;7:295–298.
   PubMed Web of Science ®Google Scholar
• Papatsoris AG, Papapetropoulos S, Singer C, et al. Urinary and erectile dysfunction in multiple system atrophy (MSA). Neurourol Urodyn. 2008;27:22–27.
   PubMed Web of Science ®Google Scholar
• Pavy-Le Traon A, Piedvache A, Perez-Lloret S, et al. New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study. J Neurol Neurosurg Psychiatry. 2016;87:554–561.
   PubMed Web of Science ®Google Scholar
• Lipp A, Sandroni P, Ahlskog JE, et al. Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch Neurol. 2009;66:742–750.
   PubMedGoogle Scholar
• Shindo K, Tsuchiya M, Ichinose Y, et al. Vasomotor regulation in patients with multiple system atrophy. J Neural Transm (Vienna). 2017;124:477–481.
   PubMed Web of Science ®Google Scholar
• Anderson T, Luxon L, Quinn N, et al. Oculomotor function in multiple system atrophy: clinical and laboratory features in 30 patients. Mov Disord. 2008;23:977–984.
   PubMed Web of Science ®Google Scholar
• Videnovic A. Management of sleep disorders in Parkinson’s disease and multiple system atrophy. Mov Disord. 2017;32:659–668.
   PubMed Web of Science ®Google Scholar
• Moreno-Lopez C, Santamaria J, Salamero M, et al. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study). Arch Neurol. 2011;68:223–230.
   PubMedGoogle Scholar
• Palma JA, Fernandez-Cordon C, Coon EA, et al. Prevalence of REM sleep behavior disorder in multiple system atrophy: a multicenter study and meta-analysis. Clin Auton Res. 2015;25:69–75.
   PubMed Web of Science ®Google Scholar
• Iranzo A, Santamaria J, Rye DB, et al. Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology. 2005;65:247–252.
   PubMed Web of Science ®Google Scholar
• Ghorayeb I, Dupouy S, Tison F, et al. Restless legs syndrome in multiple system atrophy. J Neural Transm (Vienna). 2014;121:1523–1527.
   PubMed Web of Science ®Google Scholar
• Ghorayeb I, Bioulac B, Tison F. Relationship between stridor and sleep apnoea syndrome: is it as simple as that? J Neurol Neurosurg Psychiatry. 2004;75:512–513.
   PubMed Web of Science ®Google Scholar
• Ohshima Y, Nakayama H, Matsuyama N, et al. Natural course and potential prognostic factors for sleep-disordered breathing in multiple system atrophy. Sleep Med. 2017;34:13–17.
   PubMed Web of Science ®Google Scholar
• Shimohata T, Aizawa N, Nakayama H, et al. Mechanisms and prevention of sudden death in multiple system atrophy. Parkinsonism Relat Disord. 2016;30:1–6.
   PubMed Web of Science ®Google Scholar
• Silber MH, Levine S. Stridor and death in multiple system atrophy. Mov Disord. 2000;15:699–704.
   PubMed Web of Science ®Google Scholar
• Bak TH, Caine D, Hearn VC, et al. Visuospatial functions in atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry. 2006;77:454–456.
   PubMed Web of Science ®Google Scholar
• Burk K, Daum I, Rub U. Cognitive function in multiple system atrophy of the cerebellar type. Mov Disord. 2006;21:772–776.
   PubMed Web of Science ®Google Scholar
• Fiorenzato E, Weis L, Seppi K, et al. Brain structural profile of multiple system atrophy patients with cognitive impairment. J Neural Transm (Vienna). 2017;124:293–302.
   PubMed Web of Science ®Google Scholar
• Roncevic D, Palma JA, Martinez J, et al. Cerebellar and parkinsonian phenotypes in multiple system atrophy: similarities, differences and survival. J Neural Transm. 2014;121:507–512.
   PubMed Web of Science ®Google Scholar
• Figueroa JJ, Singer W, Parsaik A, et al. Multiple system atrophy: prognostic indicators of survival. Mov Disord. 2014;29:1151–1157.
   PubMed Web of Science ®Google Scholar
• Koga S, Aoki N, Uitti RJ, et al. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology. 2015;85:404–412.
   PubMed Web of Science ®Google Scholar
• Matsushima M, Yabe I, Takahashi I, et al. Validity and reliability of a pilot scale for assessment of multiple system atrophy symptoms. Cerebellum Ataxias. 2017;4:11.
   PubMedGoogle Scholar
• Kim HJ, Jeon BS, Jellinger KA. Diagnosis and differential diagnosis of MSA: boundary issues. J Neurol. 2015;262:1801–1813.
   PubMed Web of Science ®Google Scholar
• Kim HJ, Stamelou M, Jeon B. Multiple system atrophy-mimicking conditions: diagnostic challenges. Parkinsonism Relat Disord. 2016;22(Suppl 1):S12–5.
   PubMed Web of Science ®Google Scholar
• Mestre TA, Gupta A, Lang AE. MRI signs of multiple system atrophy preceding the clinical diagnosis: the case for an imaging-supported probable MSA diagnostic category. J Neurol Neurosurg Psychiatry. 2016;87:443–444.
   PubMed Web of Science ®Google Scholar
• Rizzo G, Copetti M, Arcuti S, et al. Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. Neurology. 2016;86:566–576.
   PubMed Web of Science ®Google Scholar
• Krismer F, Jellinger KA, Scholz SW, et al. Multiple system atrophy as emerging template for accelerated drug discovery in alpha-synucleinopathies. Parkinsonism Relat Disord. 2014;20:793–799.
   PubMed Web of Science ®Google Scholar
• Kanazawa M, Tada M, Onodera O, et al. Early clinical features of patients with progressive supranuclear palsy with predominant cerebellar ataxia. Parkinsonism Relat Disord. 2013;19:1149–1151.
   PubMed Web of Science ®Google Scholar
• Joutsa J, Gardberg M, Roytta M, et al. Diagnostic accuracy of parkinsonism syndromes by general neurologists. Parkinsonism Relat Disord. 2014;20:840–844.
   PubMed Web of Science ®Google Scholar
• Osaki Y, Ben-Shlomo Y, Lees AJ, et al. A validation exercise on the new consensus criteria for multiple system atrophy. Mov Disord. 2009;24:2272–2276.
   PubMed Web of Science ®Google Scholar
• Antenora A, Rinaldi C, Roca A, et al. The multiple faces of spinocerebellar ataxia type 2. Ann Clin Transl Neurol. 2017;4:687–695.
   PubMed Web of Science ®Google Scholar
• Kim HJ, Jeon BS, Shin J, et al. Should genetic testing for SCAs be included in the diagnostic workup for MSA? Neurology. 2014;83:1733–1738.
   PubMed Web of Science ®Google Scholar
• Kamm C, Healy DG, Quinn NP, et al. The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group. Brain. 2005;128:1855–1860.
   PubMed Web of Science ®Google Scholar
• Ogaki K, Koga S, Aoki N, et al. Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review. Neuropathology 2016;36:64–76
   Google Scholar
• Algarni MA, Stoessl AJ. The role of biomarkers and imaging in Parkinson’s disease. Expert Rev Neurother. 2016;16:187–203.
   PubMed Web of Science ®Google Scholar
• Delenclos M, Jones DR, McLean PJ, et al. Biomarkers in Parkinson’s disease: advances and strategies. Parkinsonism Relat Disord. 2016;22(Suppl 1):S106–10.
   PubMed Web of Science ®Google Scholar
• Kang JH, Korecka M, Figurski MJ, et al. The Alzheimer’s disease neuroimaging initiative 2 biomarker core: a review of progress and plans. Alzheimers Dement. 2015;11:772–791.
   PubMed Web of Science ®Google Scholar
• Majbour NK, Vaikath NN, Van Dijk KD, et al. Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease. Mol Neurodegener. 2016;11:7.
   PubMed Web of Science ®Google Scholar
• Molinuevo JL, Blennow K, Dubois B, et al. The clinical use of cerebrospinal fluid biomarker testing for Alzheimer’s disease diagnosis: a consensus paper from the Alzheimer’s biomarkers standardization initiative. Alzheimers Dement. 2014;10:808–817.
   PubMed Web of Science ®Google Scholar
• Mollenhauer B, Parnetti L, Rektorova I, et al. Biological confounders for the values of cerebrospinal fluid proteins in Parkinson’s disease and related disorders. J Neurochem. 2016;139(Suppl 1):290–317.
   PubMed Web of Science ®Google Scholar
• Parnetti L, Cicognola C, Eusebi P, et al. Value of cerebrospinal fluid alpha-synuclein species as biomarker in Parkinson’s diagnosis and prognosis. Biomark Med. 2016;10:35–49.
   PubMed Web of Science ®Google Scholar
• Simonsen AH, Kuiperij B, El-Agnaf OM, et al. The utility of alpha-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature. Biomark Med. 2016;10:19–34.
   PubMed Web of Science ®Google Scholar
• Saeed U, Compagnone J, Aviv RI, et al. Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes: current and emerging concepts. Transl Neurodegener. 2017;6:8.
   PubMed Web of Science ®Google Scholar
• Magdalinou NK, Noyce AJ, Pinto R, et al. Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics. Parkinsonism Relat Disord. 2017;37:65–71.
   PubMed Web of Science ®Google Scholar
• Arneric SP, Batrla-Utermann R, Beckett L, et al. Cerebrospinal fluid biomarkers for Alzheimer’s disease: a view of the regulatory science qualification landscape from the Coalition Against Major Diseases CSF biomarker team. J Alzheimers Dis. 2017;55:19–35.
   PubMed Web of Science ®Google Scholar
• Bao W, Jia H, Finnema S, et al. PET imaging for early detection of Alzheimer’s disease: from pathologic to physiologic biomarkers. PET Clin. 2017;12:329–350.
   PubMed Web of Science ®Google Scholar
• Frisoni GB, Boccardi M, F B, et al. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol. 2017;16:661–676.
   PubMed Web of Science ®Google Scholar
• Gupta VB, Hone E, Pedrini S, et al. Altered levels of blood proteins in Alzheimer’s disease longitudinal study: results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort. Alzheimers Dement (Amst). 2017;8:60–72.
   PubMedGoogle Scholar
• Gwinn K, David KK, Swanson-Fischer C, et al. Parkinson’s disease biomarkers: perspective from the NINDS Parkinson’s Disease Biomarkers Program. Biomark Med. 2017;11:451–473.
   PubMed Web of Science ®Google Scholar
• El Kadmiri N, Said N, Slassi I, et al. Biomarkers for Alzheimer disease: classical and novel candidates’ review. Neuroscience. 2017;online Jul 17: doi 10.1016/j.neuroscience.2017.1007.1017.
   PubMedGoogle Scholar
• Mantzavinosa V, Alexiou A, Greig NH, et al. Biomarkers for Alzheimer’s disease diagnosis. Curr Alzheimer Res. 2017;14:1149–1154.
   PubMed Web of Science ®Google Scholar
• Olsson B, Schott JM, Blennow K, et al. The use of cerebrospinal fluid biomarkers to measure change in neurodegeneration in Alzheimer’s disease clinical trials. Expert Rev Neurother. 2017;17:767–775.
   PubMed Web of Science ®Google Scholar
• Sharma S, Lipincott W. Biomarkers in Alzheimer’s disease-recent update. Curr Alzheimer Res. 2017 Feb 20. doi: 10.2174/1567205014666170220141822.
   Google Scholar
• Lewczuk P, Riederer P, O’Bryant S, et al. Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry. 2017. submitted.
   PubMedGoogle Scholar
• Simonsen AH, Herukka SK, Andreasen N, et al. Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia. Alzheimers Dement. 2017;13:274–284.
   PubMed Web of Science ®Google Scholar
• Trojanowski JQ, Growdon JH A new consensus report on biomarkers for the early antemortem diagnosis of Alzheimer disease: current status, relevance to drug discovery, and recommendations for future research. J Neuropathol Exp Neurol 1998;57:643–644
   Google Scholar
• Andersen AD, Binzer M, Stenager E, et al. Cerebrospinal fluid biomarkers for Parkinson’s disease - a systematic review. Acta Neurol Scand. 2017;135:34–56.
   PubMed Web of Science ®Google Scholar
• Laurens B, Constantinescu R, Freeman R, et al. Fluid biomarkers in multiple system atrophy: a review of the MSA Biomarker Initiative. Neurobiol Dis. 2015;80:29–41.
   PubMed Web of Science ®Google Scholar
• Levin J, Maass S, Schuberth M, et al. Multiple system atrophy. In: Falup-Pecurariu C, Ferreira J, Martinez-Martin P, et al., Eds. Movement disorders curricula. Wien: Springer; 2017. p. 183–192.
   Google Scholar
• Krismer F, Pinter B, Mueller C, et al. Sniffing the diagnosis: olfactory testing in neurodegenerative parkinsonism. Parkinsonism Relat Disord. 2017;35:36–41.
   PubMed Web of Science ®Google Scholar
• Abele M, Riet A, Hummel T, et al. Olfactory dysfunction in cerebellar ataxia and multiple system atrophy. J Neurol. 2003;250:1453–1455.
   PubMed Web of Science ®Google Scholar
• Brooks SH, Klier EM, Red SD, et al. Slowed prosaccades and increased antisaccade errors as a potential behavioral biomarker of multiple system atrophy. Front Neurol. 2017;8:261.
   PubMed Web of Science ®Google Scholar
• Terao Y, Fukuda H, Tokushige S, et al. Is multiple system atrophy with cerebellar ataxia (MSA-C) like spinocerebellar ataxia and multiple system atrophy with parkinsonism (MSA-P) like Parkinson’s disease? - A saccade study on pathophysiology. Clin Neurophysiol. 2016;127:1491–1502.
   PubMed Web of Science ®Google Scholar
• Low PA, Tomalia VA, Park KJ. Autonomic function tests: some clinical applications. J Clin Neurol. 2013;9:1–8.
   PubMed Web of Science ®Google Scholar
• Vodusek DB. How to diagnose MSA early: the role of sphincter EMG. J Neural Transm (Vienna). 2005;112:1657–1668.
   PubMed Web of Science ®Google Scholar
• Ding Y, Hu YQ, Zhan SQ, et al. Comparison study of polysomnographic features in multiple system atrophy-cerebellar types combined with and without rapid eye movement sleep behavior disorder. Chin Med J (Engl). 2016;129:2173–2177.
   PubMed Web of Science ®Google Scholar
• Schrag A, Sheikh S, Quinn NP, et al. A comparison of depression, anxiety, and health status in patients with progressive supranuclear palsy and multiple system atrophy. Mov Disord. 2010;25:1077–1081.
   PubMed Web of Science ®Google Scholar
• Burton EJ, McKeith IG, Burn DJ, et al. Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain. 2004;127:791–800.
   PubMed Web of Science ®Google Scholar
• Summerfield C, Junque C, Tolosa E, et al. Structural brain changes in Parkinson disease with dementia: a voxel-based morphometry study. Arch Neurol. 2005;62:281–285.
   PubMedGoogle Scholar
• Chen S, Tan HY, Wu ZH, et al. Imaging of olfactory bulb and gray matter volumes in brain areas associated with olfactory function in patients with Parkinson’s disease and multiple system atrophy. Eur J Radiol. 2014;83:564–570.
   PubMed Web of Science ®Google Scholar
• Schulz JB, Skalej M, Wedekind D, et al. Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson’s syndrome from multiple system atrophy and progressive supranuclear palsy. Ann Neurol. 1999;45:65–74.
   PubMed Web of Science ®Google Scholar
• Pitcher TL, Melzer TR, Macaskill MR, et al. Reduced striatal volumes in Parkinson’s disease: a magnetic resonance imaging study. Transl Neurodegener. 2012;1:17.
   PubMedGoogle Scholar
• Peran P, Cherubini A, Assogna F, et al. Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature. Brain. 2010;133:3423–3433.
   PubMed Web of Science ®Google Scholar
• Wieler M, Gee M, Camicioli R, et al. Freezing of gait in early Parkinson’s disease: nigral iron content estimated from magnetic resonance imaging. J Neurol Sci. 2016;361:87–91.
   PubMed Web of Science ®Google Scholar
• Boelmans K, Bodammer NC, Suchorska B, et al. Diffusion tensor imaging of the corpus callosum differentiates corticobasal syndrome from Parkinson’s disease. Parkinsonism Relat Disord. 2010;16:498–502.
   PubMed Web of Science ®Google Scholar
• Cochrane CJ, Ebmeier KP. Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis. Neurology. 2013;80:857–864.
   PubMed Web of Science ®Google Scholar
• Vaillancourt DE, Spraker MB, Prodoehl J, et al. High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology. 2009;72:1378–1384.
   PubMed Web of Science ®Google Scholar
• Scherfler C, Schocke MF, Seppi K, et al. Voxel-wise analysis of diffusion weighted imaging reveals disruption of the olfactory tract in Parkinson’s disease. Brain. 2006;129:538–542.
   PubMed Web of Science ®Google Scholar
• Rolheiser TM, Fulton HG, Good KP, et al. Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson’s disease. J Neurol. 2011;258:1254–1260.
   PubMed Web of Science ®Google Scholar
• Meijer FJ, Steens SC, Van Rumund A, et al. Nigrosome-1 on susceptibility weighted imaging to differentiate Parkinson’s disease from atypical parkinsonism: an in vivo and ex vivo pilot study. Pol J Radiol. 2016;81:363–369.
   PubMed Web of Science ®Google Scholar
• Firbank MJ, Harrison RM, O’Brien JT. A comprehensive review of proton magnetic resonance spectroscopy studies in dementia and Parkinson’s disease. Dement Geriatr Cogn Disord. 2002;14:64–76.
   PubMed Web of Science ®Google Scholar
• Camicioli RM, Hanstock CC, Bouchard TP, et al. Magnetic resonance spectroscopic evidence for presupplementary motor area neuronal dysfunction in Parkinson’s disease. Mov Disord. 2007;22:382–386.
   PubMed Web of Science ®Google Scholar
• Taylor-Robinson SD, Turjanski N, Bhattacharya S, et al. A proton magnetic resonance spectroscopy study of the striatum and cerebral cortex in Parkinson’s disease. Metab Brain Dis. 1999;14:45–55.
   PubMed Web of Science ®Google Scholar
• Tha KK, Terae S, Tsukahara A, et al. Hyperintense putaminal rim at 1.5 T: prevalence in normal subjects and distinguishing features from multiple system atrophy. BMC Neurol. 2012;12:39.
   PubMed Web of Science ®Google Scholar
• Ramli N, Nair SR, Ramli NM, et al. Differentiating multiple-system atrophy from Parkinson’s disease. Clin Radiol. 2015;70:555–564.
   PubMed Web of Science ®Google Scholar
• Feng JY, Huang B, Yang WQ, et al. The putaminal abnormalities on 3.0T magnetic resonance imaging: can they separate parkinsonism-predominant multiple system atrophy from Parkinson’s disease? Acta Radiol. 2015;56:322–328.
   PubMed Web of Science ®Google Scholar
• Kasahara S, Miki Y, Kanagaki M, et al. “Hot cross bun” sign in multiple system atrophy with predominant cerebellar ataxia: a comparison between proton density-weighted imaging and T2-weighted imaging. Eur J Radiol. 2012;81:2848–2852.
   PubMed Web of Science ®Google Scholar
• Massey LA, Micallef C, Paviour DC, et al. Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy. Mov Disord. 2012;27:1754–1762.
   PubMed Web of Science ®Google Scholar
• Brooks DJ, Seppi K. Proposed neuroimaging criteria for the diagnosis of multiple system atrophy. Mov Disord. 2009;24:949–964.
   PubMed Web of Science ®Google Scholar
• Sako W, Murakami N, Izumi Y, et al. The difference in putamen volume between MSA and PD: evidence from a meta-analysis. Parkinsonism Relat Disord. 2014;20:873–877.
   PubMed Web of Science ®Google Scholar
• Brenneis C, Seppi K, Schocke MF, et al. Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. Mov Disord. 2003;18:1132–1138.
   PubMed Web of Science ®Google Scholar
• Barbagallo G, Sierra-Pena M, Nemmi F, et al. Multimodal MRI assessment of nigro-striatal pathway in multiple system atrophy and Parkinson disease. Mov Disord. 2016;31:325–334.
   PubMed Web of Science ®Google Scholar
• Meijer FJ, Van Rumund A, Tuladhar AM, et al. Conventional 3T brain MRI and diffusion tensor imaging in the diagnostic workup of early stage parkinsonism. Neuroradiology. 2015;57:655–669.
   PubMed Web of Science ®Google Scholar
• Ito M, Watanabe H, Kawai Y, et al. Usefulness of combined fractional anisotropy and apparent diffusion coefficient values for detection of involvement in multiple system atrophy. J Neurol Neurosurg Psychiatry. 2007;78:722–728.
   PubMed Web of Science ®Google Scholar
• Oishi K, Konishi J, Mori S, et al. Reduced fractional anisotropy in early-stage cerebellar variant of multiple system atrophy. J Neuroimaging. 2009;19:127–131.
   PubMed Web of Science ®Google Scholar
• Shiga K, Yamada K, Yoshikawa K, et al. Local tissue anisotropy decreases in cerebellopetal fibers and pyramidal tract in multiple system atrophy. J Neurol. 2005;252:589–596.
   PubMed Web of Science ®Google Scholar
• Pellecchia MT, Barone P, Mollica C, et al. Diffusion-weighted imaging in multiple system atrophy: a comparison between clinical subtypes. Mov Disord. 2009;24:689–696.
   PubMed Web of Science ®Google Scholar
• Blain CR, Barker GJ, Jarosz JM, et al. Measuring brain stem and cerebellar damage in parkinsonian syndromes using diffusion tensor MRI. Neurology. 2006;67:2199–2205.
   PubMed Web of Science ®Google Scholar
• Watanabe H, Fukatsu H, Katsuno M, et al. Multiple regional 1H-MR spectroscopy in multiple system atrophy: NAA/Cr reduction in pontine base as a valuable diagnostic marker. J Neurol Neurosurg Psychiatry. 2004;75:103–109.
   PubMed Web of Science ®Google Scholar
• Plotkin M, Amthauer H, Klaffke S, et al. Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm (Vienna). 2005;112:677–692.
   PubMed Web of Science ®Google Scholar
• Im JH, Chung SJ, Kim JS, et al. Differential patterns of dopamine transporter loss in the basal ganglia of progressive supranuclear palsy and Parkinson’s disease: analysis with [(123)I]IPT single photon emission computed tomography. J Neurol Sci. 2006;244:103–109.
   PubMed Web of Science ®Google Scholar
• Klaffke S, Kuhn AA, Plotkin M, et al. Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration. Mov Disord. 2006;21:1724–1727.
   PubMed Web of Science ®Google Scholar
• Politis M. Neuroimaging in Parkinson disease: from research setting to clinical practice. Nat Rev Neurol. 2014;10:708–722.
   PubMed Web of Science ®Google Scholar
• O’Brien JT, Colloby S, Fenwick J, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol. 2004;61:919–925.
   PubMed Web of Science ®Google Scholar
• Walker Z, Costa DC, Walker RW, et al. Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry. 2002;73:134–140.
   PubMed Web of Science ®Google Scholar
• Kim YJ, Ichise M, Ballinger JR, et al. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord. 2002;17:303–312.
   PubMed Web of Science ®Google Scholar
• Brucke T, Asenbaum S, Pirker W, et al. Measurement of the dopaminergic degeneration in Parkinson’s disease with [123I] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. J Neural Transm Suppl. 1997;50:9–24.
   PubMedGoogle Scholar
• Niccolini F, Politis M. A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism. Eur J Nucl Med Mol Imaging. 2016;43:2244–2254.
   PubMed Web of Science ®Google Scholar
• Van Royen E, Verhoeff NF, Speelman JD, et al. Multiple system atrophy and progressive supranuclear palsy. Diminished striatal D2 dopamine receptor activity demonstrated by 123I-IBZM single photon emission computed tomography. Arch Neurol. 1993;50:513–516.
   PubMedGoogle Scholar
• Ichise M, Kim YJ, Ballinger JR, et al. SPECT imaging of pre- and postsynaptic dopaminergic alterations in L-dopa-untreated PD. Neurology. 1999;52:1206–1214.
   PubMed Web of Science ®Google Scholar
• Pirker S, Perju-Dumbrava L, Kovacs GG, et al. Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed corticobasal degeneration. Parkinsonism Relat Disord. 2013;19:222–226.
   PubMed Web of Science ®Google Scholar
• Brooks DJ, Ibanez V, Sawle GV, et al. Differing patterns of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol. 1990;28:547–555.
   PubMed Web of Science ®Google Scholar
• Ghaemi M, Hilker R, Rudolf J, et al. Differentiating multiple system atrophy from Parkinson’s disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging. J Neurol Neurosurg Psychiatry. 2002;73:517–523.
   PubMed Web of Science ®Google Scholar
• Antonini A, Schwarz J, Oertel WH, et al. [11C]raclopride and positron emission tomography in previously untreated patients with Parkinson’s disease: influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors. Neurology. 1994;44:1325–1329.
   PubMed Web of Science ®Google Scholar
• Rinne UK, Laihinen A, Rinne JO, et al. Positron emission tomography demonstrates dopamine D2 receptor supersensitivity in the striatum of patients with early Parkinson’s disease. Mov Disord. 1990;5:55–59.
   PubMed Web of Science ®Google Scholar
• Brooks DJ, Ibanez V, Sawle GV, et al. Striatal D2 receptor status in patients with Parkinson’s disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography. Ann Neurol. 1992;31:184–192.
   PubMed Web of Science ®Google Scholar
• Antonini A, Leenders KL, Vontobel P, et al. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson’s disease. Brain. 1997;120(Pt 12):2187–2195.
   PubMed Web of Science ®Google Scholar
• Edison P, Rowe CC, Rinne JO, et al. Amyloid load in Parkinson’s disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry. 2008;79:1331–1338.
   PubMed Web of Science ®Google Scholar
• Gomperts SN, Locascio JJ, Marquie M, et al. Brain amyloid and cognition in Lewy body diseases. Mov Disord. 2012;27:965–973.
   PubMed Web of Science ®Google Scholar
• Foster ER, Campbell MC, Burack MA, et al. Amyloid imaging of Lewy body-associated disorders. Mov Disord. 2010;25:2516–2523.
   PubMed Web of Science ®Google Scholar
• Donaghy P, Thomas AJ, O’Brien JT. Amyloid PET Imaging in Lewy body disorders. Am J Geriatr Psychiatry. 2015;23:23–37.
   PubMed Web of Science ®Google Scholar
• Perez-Soriano A, Arena JE, Dinelle K, et al. PBB3 imaging in Parkinsonian disorders: evidence for binding to tau and other proteins. Mov Disord. 2017;32:1016–1024.
   PubMed Web of Science ®Google Scholar
• Ono M, Sahara N, Kumata K, et al. Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies. Brain. 2017;140:764–780.
   PubMed Web of Science ®Google Scholar
• Hansen AK, Knudsen K, Lillethorup TP, et al. In vivo imaging of neuromelanin in Parkinson’s disease using 18F-AV-1451 PET. Brain. 2016;139:2039–2049.
   PubMed Web of Science ®Google Scholar
• Koga S, Ono M, Sahara N, et al. Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to alpha-synuclein pathology. Mov Disord. 2017;32:884–892.
   PubMed Web of Science ®Google Scholar
• Gerhard A, Banati RB, Goerres GB, et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003;61:686–689.
   PubMed Web of Science ®Google Scholar
• Gerhard A, Pavese N, Hotton G, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis. 2006;21:404–412.
   PubMed Web of Science ®Google Scholar
• Ouchi Y, Yoshikawa E, Sekine Y, et al. Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol. 2005;57:168–175.
   PubMed Web of Science ®Google Scholar
• Edison P, Ahmed I, Fan Z, et al. Microglia, amyloid, and glucose metabolism in Parkinson’s disease with and without dementia. Neuropsychopharmacology. 2013;38:938–949.
   PubMed Web of Science ®Google Scholar
• Gerhard A, Watts J, Trender-Gerhard I, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration. Mov Disord. 2004;19:1221–1226.
   PubMed Web of Science ®Google Scholar
• Fan Z, Aman Y, Ahmed I, et al. Influence of microglial activation on neuronal function in Alzheimer’s and Parkinson’s disease dementia. Alzheimers Dement. 2015;11(608–21):e7.
   Google Scholar
• Oka H, Toyoda C, Yogo M, et al. Cardiovascular dysautonomia in de novo Parkinson’s disease without orthostatic hypotension. Eur J Neurol. 2011;18:286–292.
   PubMed Web of Science ®Google Scholar
• Taki J, Nakajima K, Hwang EH, et al. Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific. [email protected]. Eur J Nucl Med. 2000;27:566–573.
   PubMedGoogle Scholar
• Takatsu H, Nishida H, Matsuo H, et al. Cardiac sympathetic denervation from the early stage of Parkinson’s disease: clinical and experimental studies with radiolabeled MIBG. J Nucl Med. 2000;41:71–77.
   PubMed Web of Science ®Google Scholar
• Taki J, Yoshita M, Yamada M, et al. Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: it can be a specific marker for Lewy body disease. Ann Nucl Med. 2004;18:453–461.
   PubMed Web of Science ®Google Scholar
• Hanyu H, Shimizu S, Hirao K, et al. The role of 123I-metaiodobenzylguanidine myocardial scintigraphy in the diagnosis of Lewy body disease in patients with dementia in a memory clinic. Dement Geriatr Cogn Disord. 2006;22:379–384.
   PubMed Web of Science ®Google Scholar
• Berg D, Siefker C, Becker G. Echogenicity of the substantia nigra in Parkinson’s disease and its relation to clinical findings. J Neurol. 2001;248:684–689.
   PubMed Web of Science ®Google Scholar
• Walter U, Dressler D, Probst T, et al. Transcranial brain sonography findings in discriminating between parkinsonism and idiopathic Parkinson disease. Arch Neurol. 2007;64:1635–1640.
   PubMedGoogle Scholar
• Gaenslen A, Unmuth B, Godau J, et al. The specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson’s disease: a prospective blinded study. Lancet Neurol. 2008;7:417–424.
   PubMed Web of Science ®Google Scholar
• Walter U, Dressler D, Wolters A, et al. Sonographic discrimination of dementia with Lewy bodies and Parkinson’s disease with dementia. J Neurol. 2006;253:448–454.
   PubMed Web of Science ®Google Scholar
• Walter U, Dressler D, Wolters A, et al. Sonographic discrimination of corticobasal degeneration vs progressive supranuclear palsy. Neurology. 2004;63:504–509.
   PubMed Web of Science ®Google Scholar
• Sadowski K, Serafin-Krol M, Szlachta K, et al. Basal ganglia echogenicity in tauopathies. J Neural Transm (Vienna). 2015;122:863–865.
   PubMed Web of Science ®Google Scholar
• Ebentheuer J, Canelo M, Trautmann E, et al. Substantia nigra echogenicity in progressive supranuclear palsy. Mov Disord. 2010;25:773–777.
   PubMed Web of Science ®Google Scholar
• Behnke S, Berg D, Naumann M, et al. Differentiation of Parkinson’s disease and atypical parkinsonian syndromes by transcranial ultrasound. J Neurol Neurosurg Psychiatry. 2005;76:423–425.
   PubMed Web of Science ®Google Scholar
• Heller J, Brcina N, Dogan I, et al. Brain imaging findings in idiopathic REM sleep behavior disorder (RBD) – a systematic review on potential biomarkers for neurodegeneration. Sleep Med Rev. 2017;34:23–33.
   PubMed Web of Science ®Google Scholar
• Pradhan S, Tandon R. Relevance of non-specific MRI features in multiple system atrophy. Clin Neurol Neurosurg. 2017;159:29–33.
   PubMed Web of Science ®Google Scholar
• Matsusue E, Fujii S, Kanasaki Y, et al. Putaminal lesion in multiple system atrophy: postmortem MR-pathological correlations. Neuroradiology. 2008;50:559–567.
   PubMed Web of Science ®Google Scholar
• Sugiyama A, Ito S, Suichi T, et al. Putaminal hypointensity on T2*-weighted MR imaging is the most practically useful sign in diagnosing multiple system atrophy: a preliminary study. J Neurol Sci. 2015;349:174–178.
   PubMed Web of Science ®Google Scholar
• Lee JH, Kim TH, Mun CW, et al. Progression of subcortical atrophy and iron deposition in multiple system atrophy: a comparison between clinical subtypes. J Neurol. 2015;262:1876–1882.
   PubMed Web of Science ®Google Scholar
• Deguchi K, Ikeda K, Kume K, et al. Significance of the hot-cross bun sign on T2*-weighted MRI for the diagnosis of multiple system atrophy. J Neurol. 2015;262:1433–1439.
   PubMed Web of Science ®Google Scholar
• Wadia PM, Howard P, Ribeirro MQ, et al. The value of GRE, ADC and routine MRI in distinguishing Parkinsonian disorders. Can J Neurol Sci. 2013;40:389–402.
   PubMed Web of Science ®Google Scholar
• Hwang I, Sohn CH, Kang KM, et al. Differentiation of parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease using 3T susceptibility-weighted MR imaging, focusing on putaminal change and lesion asymmetry. AJNR Am J Neuroradiol. 2015;36:2227–2234.
   PubMed Web of Science ®Google Scholar
• Schwarz ST, Afzal M, Morgan PS, et al. The ‘swallow tail’ appearance of the healthy nigrosome – a new accurate test of Parkinson’s disease: a case-control and retrospective cross-sectional MRI study at 3T. PLoS One. 2014;9:e93814.
   PubMed Web of Science ®Google Scholar
• Wang N, Yang H, Li C, et al. Using ‘swallow-tail’ sign and putaminal hypointensity as biomarkers to distinguish multiple system atrophy from idiopathic Parkinson’s disease: a susceptibility-weighted imaging study. Eur Radiol. 2017;27:3174–3180.
   PubMed Web of Science ®Google Scholar
• Wang PS, Yeh CL, Lu CF, et al. The involvement of supratentorial white matter in multiple system atrophy: a diffusion tensor imaging tractography study. Acta Neurol Belg. 2017;117:213–220.
   PubMed Web of Science ®Google Scholar
• De Marzi R, Bajaj S, Krismer F, et al. Putaminal diffusion imaging for the differential diagnosis of the parkinsoniao variant of multiple system atrophy from Parkinson’s disease: impact of segmentation accuracy (abstr.). NeuroLogisch. 2017;Suppl 1:8–9.
   Google Scholar
• Planetta PJ, Kurani AS, Shukla P, et al. Distinct functional and macrostructural brain changes in Parkinson’s disease and multiple system atrophy. Hum Brain Mapp. 2015;36:1165–1179.
   PubMed Web of Science ®Google Scholar
• Krismer F, Wenning GK. Investigations. In: Wenning GK, Fanciulli A, Eds. Multiple system atrophy. Vienna: Springer-Verlag; 2014. p. 143–168.
   Google Scholar
• Hara D, Maki F, Tanaka S, et al. MRI-based cerebellar volume measurements correlate with the International Cooperative Ataxia Rating Scale score in patients with spinocerebellar degeneration or multiple system atrophy. Cerebellum Ataxias. 2016;3:14.
   PubMedGoogle Scholar
• Guevara C, Bulatova K, Soruco W, et al. Retrospective diagnosis of parkinsonian syndromes using whole-brain atrophy rates. Front Aging Neurosci. 2017;9:99.
   PubMed Web of Science ®Google Scholar
• Focke NK, Helms G, Pantel PM, et al. Differentiation of typical and atypical Parkinson syndromes by quantitative MR imaging. AJNR Am J Neuroradiol. 2011;32:2087–2092.
   PubMed Web of Science ®Google Scholar
• Wang Y, Butros SR, Shuai X, et al. Different iron-deposition patterns of multiple system atrophy with predominant parkinsonism and idiopathetic Parkinson diseases demonstrated by phase-corrected susceptibility-weighted imaging. AJNR Am J Neuroradiol. 2012;33:266–273.
   PubMed Web of Science ®Google Scholar
• Cnyrim CD, Kupsch A, Ebersbach G, et al. Diffusion tensor imaging in idiopathic Parkinson’s disease and multisystem atrophy (Parkinsonian type). Neurodegener Dis. 2014;13:1–8.
   PubMed Web of Science ®Google Scholar
• Chen B, Fan G, Sun W, et al. Usefulness of diffusion-tensor MRI in the diagnosis of Parkinson variant of multiple system atrophy and Parkinson’s disease: a valuable tool to differentiate between them? Clin Radiol. 2017;72:610e9–610 e15.
   Web of Science ®Google Scholar
• Worker A, Blain C, Jarosz J, et al. Diffusion tensor imaging of Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study. PLoS One. 2014;9:e112638.
   PubMed Web of Science ®Google Scholar
• Sako W, Murakami N, Izumi Y, et al. The difference of apparent diffusion coefficient in the middle cerebellar peduncle among parkinsonian syndromes: evidence from a meta-analysis. J Neurol Sci. 2016;363:90–94.
   PubMed Web of Science ®Google Scholar
• Takado Y, Igarashi H, Terajima K, et al. Brainstem metabolites in multiple system atrophy of cerebellar type: 3.0-T magnetic resonance spectroscopy study. Mov Disord. 2011;26:1297–1302.
   PubMed Web of Science ®Google Scholar
• Ji L, Wang Y, Zhu D, et al. White matter differences between multiple system atrophy (parkinsonian type) and Parkinson’s disease: a diffusion tensor image study. Neuroscience. 2015;305:109–116.
   PubMed Web of Science ®Google Scholar
• Nocker M, Seppi K, Donnemiller E, et al. Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [123I]beta-CIT SPECT. Eur J Nucl Med Mol Imaging. 2012;39:1012–1020.
   PubMed Web of Science ®Google Scholar
• Perju-Dumbrava LD, Kovacs GG, Pirker S, et al. Dopamine transporter imaging in autopsy-confirmed Parkinson’s disease and multiple system atrophy. Mov Disord. 2012;27:65–71.
   PubMed Web of Science ®Google Scholar
• Kraemmer J, Kovacs GG, Perju-Dumbrava L, et al. Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts. Mov Disord. 2014;29:1767–1773.
   PubMed Web of Science ®Google Scholar
• Kim HW, Kim JS, Oh M, et al. Different loss of dopamine transporter according to subtype of multiple system atrophy. Eur J Nucl Med Mol Imaging. 2016;43:517–525.
   PubMed Web of Science ®Google Scholar
• Oh M, Kim JS, Kim JY, et al. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple-system atrophy. J Nucl Med. 2012;53:399–406.
   PubMed Web of Science ®Google Scholar
• McKinley J, O’Connell M, Farrell M, et al. Normal dopamine transporter imaging does not exclude multiple system atrophy. Parkinsonism Relat Disord. 2014;20:933–934.
   PubMed Web of Science ®Google Scholar
• Lewis SJ, Pavese N, Rivero-Bosch M, et al. Brain monoamine systems in multiple system atrophy: a positron emission tomography study. Neurobiol Dis. 2012;46:130–136.
   PubMed Web of Science ®Google Scholar
• Tsukamoto K, Matsusue E, Kanasaki Y, et al. Significance of apparent diffusion coefficient measurement for the differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and Parkinson’s disease: evaluation by 3.0-T MR imaging. Neuroradiology. 2012;54:947–955.
   PubMed Web of Science ®Google Scholar
• Brajkovic L, Kostic V, Sobic-Saranovic D, et al. The utility of FDG-PET in the differential diagnosis of Parkinsonism. Neurol Res. 2017;39:675–684.
   PubMed Web of Science ®Google Scholar
• Meyer PT, Frings L, Rucker G, et al. 18F-FDG PET in parkinsonism: differential diagnosis and cognitive impairment in Parkinson’s disease. J Nucl Med. 2017 Sept 14. online.
   Web of Science ®Google Scholar
• Tang CC, Poston KL, Eckert T, et al. Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol. 2010;9:149–158.
   PubMed Web of Science ®Google Scholar
• Poston KL, Eidelberg D. Functional brain networks and abnormal connectivity in the movement disorders. Neuroimage. 2012;62:2261–2270.
   PubMed Web of Science ®Google Scholar
• Juh R, Kim J, Moon D, et al. Different metabolic patterns analysis of Parkinsonism on the 18F-FDG PET. Eur J Radiol. 2004;51:223–233.
   PubMed Web of Science ®Google Scholar
• Eckert T, Barnes A, Dhawan V, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage. 2005;26:912–921.
   PubMed Web of Science ®Google Scholar
• Sakurai K, Imabayashi E, Ito K, et al. The utility of cerebral perfusion SPECT analysis using SPM8, eZIS and vbSEE for the diagnosis of multiple system atrophy-parkinsonism. Ann Nucl Med. 2015;29:206–213.
   PubMed Web of Science ®Google Scholar
• Baudrexel S, Seifried C, Penndorf B, et al. The value of putaminal diffusion imaging versus 18-fluorodeoxyglucose positron emission tomography for the differential diagnosis of the Parkinson variant of multiple system atrophy. Mov Disord. 2014;29:380–387.
   PubMed Web of Science ®Google Scholar
• Matsuda H, Imabayashi E, Kuji I, et al. Evaluation of both perfusion and atrophy in multiple system atrophy of the cerebellar type using brain SPECT alone. BMC Med Imaging. 2010;10:17.
   PubMedGoogle Scholar
• Coakeley SStrafella AP. Imaging tau pathology in parkinsonisms. Npj parkinsons Dis. 2017;3:22.
   PubMed Web of Science ®Google Scholar
• Cho H, Choi JY, Lee SH, et al. 18 F-AV-1451 binds to putamen in multiple system atrophy. Mov Disord. 2017;32:171–173.
   PubMed Web of Science ®Google Scholar
• Gasnier B, Roisin MP, Scherman D, et al. Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes. Mol Pharmacol. 1986;29:275–280.
   PubMed Web of Science ®Google Scholar
• Treglia G, Stefanelli A, Cason E, et al. Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson’s disease and multiple-system atrophy: a systematic review and a meta-analysis. Clin Neurol Neurosurg. 2011;113:823–829.
   PubMed Web of Science ®Google Scholar
• King AE, Mintz J, Royall DR. Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord. 2011;26:1218–1224.
   PubMed Web of Science ®Google Scholar
• Orimo S, Suzuki M, Inaba A, et al. 123I-MIBG myocardial scintigraphy for differentiating Parkinson’s disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2012;18:494–500.
   PubMed Web of Science ®Google Scholar
• Kaindlstorfer C, Krismer F, Fanciulli A, et al. Diagnostic value of cardiac 123I-MIBG SPECT and CT co-registration in PD and MSA-P (Poster). NeuroLogisch. 2016;Suppl 1:38.
   Google Scholar
• Nagayama H, Ueda M, Yamazaki M, et al. Abnormal cardiac [(123)I]-meta-iodobenzylguanidine uptake in multiple system atrophy. Mov Disord. 2010;25:1744–1747.
   PubMed Web of Science ®Google Scholar
• Orimo S, Kanazawa T, Nakamura A, et al. Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy. Acta Neuropathol. 2007;113:81–86.
   PubMed Web of Science ®Google Scholar
• Rascol O, Schelosky L. 123I-metaiodobenzylguanidine scintigraphy in Parkinson’s disease and related disorders. Mov Disord. 2009;24(Suppl 2):S732–41.
   PubMed Web of Science ®Google Scholar
• Baschieri F, Calandra-Buonaura G, Cecere A, et al. Iodine-123-meta-iodobenzylguanidine myocardial scintigraphy in isolated autonomic failure: potential red flag for future multiple system atrophy. Front Neurol. 2017;8:225.
   PubMed Web of Science ®Google Scholar
• Li X, Xue S, Jia S, et al. Transcranial sonography in idiopathic REM sleep behavior disorder and multiple system atrophy. Psychiatry Clin Neurosci. 2017;71:238–246.
   PubMed Web of Science ®Google Scholar
• Shi M, Bradner J, Hancock AM, et al. Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol. 2011;69:570–580.
   PubMed Web of Science ®Google Scholar
• Wang Y, Shi M, Chung KA, et al. Phosphorylated alpha-synuclein in Parkinson’s disease. Sci Transl Med. 2012;4:121ra20.
   PubMed Web of Science ®Google Scholar
• Hall S, Ohrfelt A, Constantinescu R, et al. Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch Neurol. 2012;69:1445–1452.
   PubMed Web of Science ®Google Scholar
• Herbert MK, Eeftens JM, Aerts MB, et al. CSF levels of DJ-1 and tau distinguish MSA patients from PD patients and controls. Parkinsonism Relat Disord. 2014;20:112–115.
   PubMed Web of Science ®Google Scholar
• Herbert MK, Aerts MB, Beenes M, et al. CSF neurofilament light chain but not FLT3 ligand discriminates Parkinsonian disorders. Front Neurol. 2015;6:91.
   PubMed Web of Science ®Google Scholar
• Magdalinou NK, Paterson RW, Schott JM, et al. A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry. 2015;86:1240–1247.
   PubMed Web of Science ®Google Scholar
• Shah A, Hiew KW, Han P, et al. Alpha-synuclein in bio fluids and tissues as a potential biomarker for Parkinson’s disease. J Alzheimers Parkinsonism Dem. 2017;2:013.
   Google Scholar
• Goldstein DS, Holmes C, Bentho O, et al. Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy. Parkinsonism Relat Disord. 2008;14:600–607.
   PubMed Web of Science ®Google Scholar
• Goldstein DS, Holmes C, Sharabi Y. Cerebrospinal fluid biomarkers of central catecholamine deficiency in Parkinson’s disease and other synucleinopathies. Brain. 2012;135:1900–1913.
   PubMed Web of Science ®Google Scholar
• Salvesen L, Bech S, Lokkegaard A, et al. The DJ-1 concentration in cerebrospinal fluid does not differentiate among Parkinsonian syndromes. Parkinsonism Relat Disord. 2012;18:899–901.
   PubMed Web of Science ®Google Scholar
• Kikuchi A, Takeda A, Onodera H, et al. Systemic increase of oxidative nucleic acid damage in Parkinson’s disease and multiple system atrophy. Neurobiol Dis. 2002;9:244–248.
   PubMed Web of Science ®Google Scholar
• Mondello S, Constantinescu R, Zetterberg H, et al. CSF alpha-synuclein and UCH-L1 levels in Parkinson’s disease and atypical parkinsonian disorders. Parkinsonism Relat Disord. 2014;20:382–387.
   PubMed Web of Science ®Google Scholar
• Silajdzic E, Constantinescu R, Holmberg B, et al. Flt3 ligand does not differentiate between Parkinsonian disorders. Mov Disord. 2014;29:1319–1322.
   PubMed Web of Science ®Google Scholar
• Wang Y, Hancock AM, Bradner J, et al. Complement 3 and factor h in human cerebrospinal fluid in Parkinson’s disease, Alzheimer’s disease, and multiple-system atrophy. Am J Pathol. 2011;178:1509–1516.
   PubMed Web of Science ®Google Scholar
• Tateno F, Sakakibara R, Kawai T, et al. Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease. Alzheimer Dis Assoc Disord. 2012;26:213–216.
   PubMed Web of Science ®Google Scholar
• Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, et al. Alpha-synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol. 2011;10:230–240.
   PubMed Web of Science ®Google Scholar
• Foulds PG, Yokota O, Thurston A, et al. Post mortem cerebrospinal fluid alpha-synuclein levels are raised in multiple system atrophy and distinguish this from the other alpha-synucleinopathies, Parkinson’s disease and Dementia with Lewy bodies. Neurobiol Dis. 2012;45:188–195.
   PubMed Web of Science ®Google Scholar
• Gao L, Tang H, Nie K, et al. Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson’s disease diagnosis: a systematic review and meta-analysis. Int J Neurosci. 2015;125:645–654.
   PubMed Web of Science ®Google Scholar
• Eusebi P, Giannandrea DBiscetti L, et al. Diagnostic utility of cerebrospinal fluid alpha-synuclein in Parkinson's disease: A systematic review and meta-analysis. Mov Disord. 2017; online Sep 7: doi doi:10.1002/mds.27110.
   Google Scholar
• Constantinescu R, Rosengren L, Johnels B, et al. Consecutive analyses of cerebrospinal fluid axonal and glial markers in Parkinson’s disease and atypical Parkinsonian disorders. Parkinsonism Relat Disord. 2010;16:142–145.
   PubMed Web of Science ®Google Scholar
• Holmberg B, Johnels B, Blennow K, et al. Cerebrospinal fluid Abeta42 is reduced in multiple system atrophy but normal in Parkinson’s disease and progressive supranuclear palsy. Mov Disord. 2003;18:186–190.
   PubMed Web of Science ®Google Scholar
• Paik MJ, Ahn YH, Lee PH, et al. Polyamine patterns in the cerebrospinal fluid of patients with Parkinson’s disease and multiple system atrophy. Clin Chim Acta. 2010;411:1532–1535.
   PubMed Web of Science ®Google Scholar
• Brouillette AM, Oz G, Gomez CM. Cerebrospinal fluid biomarkers in spinocerebellar ataxia: a pilot study. Dis Markers. 2015;2015:413098.
   PubMed Web of Science ®Google Scholar
• Süssmuth SD, Uttner I, Landwehrmeyer B, et al. Differential pattern of brain-specific CSF proteins tau and amyloid-beta in Parkinsonian syndromes. Mov Disord. 2010;25:1284–1288.
   PubMed Web of Science ®Google Scholar
• Abdo WF, Bloem BR, Van Geel WJ, et al. CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson’s disease. Neurobiol Aging. 2007;28:742–747.
   PubMed Web of Science ®Google Scholar
• Bech S, Hjermind LE, Salvesen L, et al. Amyloid-related biomarkers and axonal damage proteins in parkinsonian syndromes. Parkinsonism Relat Disord. 2012;18:69–72.
   PubMed Web of Science ®Google Scholar
• Sako W, Murakami N, Izumi Y, et al. Neurofilament light chain level in cerebrospinal fluid can differentiate Parkinson’s disease from atypical parkinsonism: evidence from a meta-analysis. J Neurol Sci. 2015;352:84–87.
   PubMed Web of Science ®Google Scholar
• Hu X, Yang Y, Gong D. Cerebrospinal fluid levels of neurofilament light chain in multiple system atrophy relative to Parkinson’s disease: a meta-analysis. Neurol Sci. 2017;38:407–414.
   PubMed Web of Science ®Google Scholar
• Abdo WF, Van De Warrenburg BP, Kremer HP, et al. CSF biomarker profiles do not differentiate between the cerebellar and parkinsonian phenotypes of multiple system atrophy. Parkinsonism Relat Disord. 2007;13:480–482.
   PubMed Web of Science ®Google Scholar
• Constantinescu R, Andreasson U, Li S, et al. Proteomic profiling of cerebrospinal fluid in parkinsonian disorders. Parkinsonism Relat Disord. 2010;16:545–549.
   PubMed Web of Science ®Google Scholar
• Petzold A, Thompson EJ, Keir G, et al. Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy. J Neurol Sci. 2009;279:76–79.
   PubMed Web of Science ®Google Scholar
• Martinez-Rodriguez JE, Seppi K, Cardozo A, et al. Cerebrospinal fluid hypocretin-1 levels in multiple system atrophy. Mov Disord. 2007;22:1822–1824.
   PubMed Web of Science ®Google Scholar
• Ishigami N, Tokuda T, Ikegawa M, et al. Cerebrospinal fluid proteomic patterns discriminate Parkinson’s disease and multiple system atrophy. Mov Disord. 2012;27:851–857.
   PubMed Web of Science ®Google Scholar
• Vallelunga A, Ragusa M, Di Mauro S, et al. Identification of circulating microRNAs for the differential diagnosis of Parkinson’s disease and multiple system atrophy. Front Cell Neurosci. 2014;8:156.
   PubMed Web of Science ®Google Scholar
• Singer W, Schmeichel A, Goldstein D, et al. Spinal fluid biomarkers for multiple system atrophy - a pilot study (abstr.). Neurology. 2016;86(Suppl):S18.002.
   PubMed Web of Science ®Google Scholar
• Marques TM, Kuiperij HB, Bruinsma IB, et al. MicroRNAs in cerebrospinal fluid as potential biomarkers for Parkinson’s disease and multiple system atrophy. Mol Neurobiol. 2016.
   Google Scholar
• Lee PH, Lee G, Park HJ, et al. The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy. J Neural Transm (Vienna). 2006;113:1435–1439.
   PubMed Web of Science ®Google Scholar
• Sun ZF, Xiang XS, Chen Z, et al. Increase of the plasma alpha-synuclein levels in patients with multiple system atrophy. Mov Disord. 2014;29:375–379.
   PubMed Web of Science ®Google Scholar
• Hansson O, Janelidze S, Hall S, et al. Blood-based NfL: a biomarker for differential diagnosis of parkinsonian disorder. Neurology. 2017;88:930–937.
   PubMed Web of Science ®Google Scholar
• Chen D, Wei X, Zou J, et al. Contra-directional expression of serum homocysteine and uric acid as important biomarkers of multiple system atrophy severity: a cross-sectional study. Front Cell Neurosci. 2015;9:247.
   PubMed Web of Science ®Google Scholar
• Zhou L, Jiang Y, Zhu C, et al. Oxidative stress and environmental exposures are associated with multiple system atrophy in Chinese patients. Can J Neurol Sci. 2016;43:703–709.
   PubMed Web of Science ®Google Scholar
• Guo Y, Zhuang XD, Xian WB, et al. Serum Klotho, vitamin D, and homocysteine in combination predict the outcomes of Chinese patients with multiple system atrophy. CNS Neurosci Ther. 2017;23:657–666.
   PubMed Web of Science ®Google Scholar
• Numao A, Suzuki K, Miyamoto M, et al. Clinical correlates of serum insulin-like growth factor-1 in patients with Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. Parkinsonism Relat Disord. 2014;20:212–216.
   PubMed Web of Science ®Google Scholar
• Pellecchia MT, Salvatore E, Pivonello R, et al. Stimulation of growth hormone release in multiple system atrophy, Parkinson’s disease and idiopathic cerebellar ataxia. Neurol Sci. 2001;22:79–80.
   PubMed Web of Science ®Google Scholar
• Pellecchia MT, Pivonello R, Longo K, et al. Multiple system atrophy is associated with changes in peripheral insulin-like growth factor system. Mov Disord. 2010;25:2621–2626.
   PubMed Web of Science ®Google Scholar
• Kasai T, Tokuda T, Ohmichi T, et al. Serum levels of coenzyme Q10 in patients with multiple system atrophy. PLoS One. 2016;11:e0147574.
   PubMed Web of Science ®Google Scholar
• Mitsui J, Matsukawa T, Yasuda T, et al. Plasma coenzyme Q10 levels in patients with multiple system atrophy. JAMA Neurol. 2016;73:977–980.
   PubMed Web of Science ®Google Scholar
• Barca E, Kleiner G, Tang G, et al. Decreased coenzyme Q10 levels in multiple system atrophy cerebellum. J Neuropathol Exp Neurol. 2016;75:663–672.
   PubMed Web of Science ®Google Scholar
• Brodacki B, Staszewski J, Toczylowska B, et al. Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFalpha, and INFgamma concentrations are elevated in patients with atypical and idiopathic parkinsonism. Neurosci Lett. 2008;441:158–162.
   PubMed Web of Science ®Google Scholar
• Kaufman E, Hall S, Surova Y, et al. Proinflammatory cytokines are elevated in serum of patients with multiple system atrophy. PLoS One. 2013;8:e62354.
   PubMed Web of Science ®Google Scholar
• Mahlknecht P, Stemberger S, Sprenger F, et al. An antibody microarray analysis of serum cytokines in neurodegenerative Parkinsonian syndromes. Proteome Sci. 2012;10:71.
   PubMed Web of Science ®Google Scholar
• Yamagishi Y, Saigoh K, Saito Y, et al. Diagnosis of Parkinson’s disease and the level of oxidized DJ-1 protein. Neurosci Res. 2017; online July 10: doi 10.1016/j.neures.2017.1006.1008.
   PubMedGoogle Scholar
• Shi M, Liu C, Cook TJ, et al. Plasma exosomal alpha-synuclein is likely CNS-derived and increased in Parkinson’s disease. Acta Neuropathol. 2014;128:639–650.
   PubMed Web of Science ®Google Scholar
• Scherzer CR, Grass JA, Liao Z, et al. GATA transcription factors directly regulate the Parkinson’s disease-linked gene alpha-synuclein. Proc Natl Acad Sci U S A. 2008;105:10907–10912.
   PubMed Web of Science ®Google Scholar
• Goldstein DS, Kopin IJ, Sharabi Y, et al. Plasma biomarkers of decreased vesicular storage distinguish Parkinson disease with orthostatic hypotension from the parkinsonian form of multiple system atrophy. Clin Auton Res. 2015;25:61–67.
   PubMed Web of Science ®Google Scholar
• Quinzii CM, Lopez LC, Naini A, et al. Human CoQ10 deficiencies. Biofactors. 2008;32:113–118.
   PubMed Web of Science ®Google Scholar
• Chen YP, Zhao B, Cao B, et al. Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy. Neurobiol Aging. 2015;36(1222):e7–11.
   Google Scholar
• Ogaki K, Fujioka S, Heckman MG, et al. Analysis of COQ2 gene in multiple system atrophy. Mol Neurodegener. 2014;9:44.
   PubMed Web of Science ®Google Scholar
• Kuo SH, Quinzii CM. Coenzyme Q10 as a peripheral biomarker for multiple system atrophy. JAMA Neurol. 2016;73:917–919.
   PubMed Web of Science ®Google Scholar
• Doppler K, Weis J, Karl K, et al. Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy. Mov Disord. 2015;30:1688–1692.
   PubMed Web of Science ®Google Scholar
• Zange L, Noack C, Hahn K, et al. Phosphorylated alpha-synuclein in skin nerve fibres differentiates Parkinson’s disease from multiple system atrophy. Brain. 2015;138:2310–2321.
   PubMed Web of Science ®Google Scholar
• Nakamura K, Mori F, Kon T, et al. Filamentous aggregations of phosphorylated alpha-synuclein in Schwann cells (Schwann cell cytoplasmic inclusions) in multiple system atrophy. Acta Neuropathol Commun. 2015;3:29.
   PubMed Web of Science ®Google Scholar
• Kuzdas-Wood D, Irschick R, Theurl M, et al. Involvement of peripheral nerves in the transgenic plp-alpha-syn model of multiple system atrophy: extending the phenotype. PLoS One. 2015;10:e0136575.
   PubMed Web of Science ®Google Scholar
• Haga R, Sugimoto K, Nishijima H, et al. Clinical utility of skin biopsy in differentiating between Parkinson’s disease and multiple system atrophy. Parkinsons Dis. 2015;2015:167038.
   PubMed Web of Science ®Google Scholar
• Mori F, Inenaga C, Yoshimoto M, et al. Alpha-synuclein immunoreactivity in normal and neoplastic Schwann cells. Acta Neuropathol. 2002;103:145–151.
   PubMed Web of Science ®Google Scholar
• Provitera V, Nolano M, Caporaso G, et al. Postganglionic sudomotor denervation in patients with multiple system atrophy. Neurology. 2014;82:2223–2229.
   PubMed Web of Science ®Google Scholar
• Chung SJ, Kim J, Lee HJ, et al. Alpha-synuclein in gastric and colonic mucosa in Parkinson’s disease: limited role as a biomarker. Mov Disord. 2016;31:241–249.
   PubMed Web of Science ®Google Scholar
• Beach TG, Adler CH, Sue LI, et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 2010;119:689–702.
   PubMed Web of Science ®Google Scholar
• Böttner M, Zorenkov D, Hellwig I, et al. Expression pattern and localization of alpha-synuclein in the human enteric nervous system. Neurobiol Dis. 2012;48:474–480.
   PubMed Web of Science ®Google Scholar
• Del Tredici K, Hawkes CH, Ghebremedhin E, et al. Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol. 2010;119:703–713.
   PubMed Web of Science ®Google Scholar
• Adler CH, Dugger BN, Hinni ML, et al. Submandibular gland needle biopsy for the diagnosis of Parkinson disease. Neurology. 2014;82:858–864.
   PubMed Web of Science ®Google Scholar
• Pouclet H, Lebouvier T, Coron E, et al. Analysis of colonic alpha-synuclein pathology in multiple system atrophy. Parkinsonism Relat Disord. 2012;18:893–895.
   PubMed Web of Science ®Google Scholar
• Valera E, Spencer B, Fields JA, et al. Combination of alpha-synuclein immunotherapy with anti-inflammatory treatment in a transgenic mouse model of multiple system atrophy. Acta Neuropathol Commun. 2017;5:2.
   PubMed Web of Science ®Google Scholar
• Valera E, Monzio Compagnoni G, Masliah E. Review: novel treatment strategies targeting alpha-synuclein in multiple system atrophy as a model of synucleinopathy. Neuropathol Appl Neurobiol. 2016;42:95–106.
   PubMed Web of Science ®Google Scholar