440
Views
0
CrossRef citations to date
0
Altmetric
Review

The Utility of α-Synuclein as Biofluid Marker in Neurodegenerative Diseases: a Systematic Review of The Literature

, , , , , , , , , & show all
Pages 19-34 | Published online: 28 Aug 2015

References

  • Del Tredici K , HawkesCH, GhebremedhinE, BraakH. Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol.119(6), 703–713 (2010).
  • Hughes AJ , DanielSE, KilfordL, LeesAJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J. Neurol. Neurosurg. Psychiatry55(3), 181–184 (1992).
  • El-Agnaf OM , SalemSA, PaleologouKEet al. Alpha-synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma. FASEB J.17(13), 1945–1947 (2003).
  • Mollenhauer B , El-AgnafOM, MarcusK, TrenkwalderC, SchlossmacherMG. Quantification of alpha-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark. Med.4(5), 683–699 (2010).
  • Ueda K , SaitohT, MoriH. Tissue-dependent alternative splicing of mRNA for NACP, the precursor of non-A beta component of Alzheimer’s disease amyloid. Biochem. Biophys. Res. Commun.205(2), 1366–1372 (1994).
  • Campion D , MartinC, HeiligRet al. The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease. Genomics26(2), 254–257 (1995).
  • Mollenhauer B , CullenV, KahnIet al. Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp. Neurol.213(2), 315–325 (2008).
  • Tokuda T , SalemSA, AllsopDet al. Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s disease. Biochem. Biophys. Res. Commun.349(1), 162–166 (2006).
  • Van Geel WJ , AbdoWF, MelisR, WilliamsS, BloemBR, VerbeekMM. A more efficient enzyme-linked immunosorbent assay for measurement of alpha-synuclein in cerebrospinal fluid. J. Neurosci. Methods168(1), 182–185 (2008).
  • Tokuda T , QureshiMM, ArdahMTet al. Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease. Neurology75(20), 1766–1772 (2010).
  • Parnetti L , ChiasseriniD, BellomoGet al. Cerebrospinal fluid Tau/alpha-synuclein ratio in Parkinson’s disease and degenerative dementias. Mov. Disord.26(8), 1428–1435 (2011).
  • Parnetti L , FarottiL, EusebiPet al. Differential role of CSF alpha-synuclein species, tau, and Abeta42 in Parkinson’s disease. Front. Aging Neurosci.6, 53 (2014).
  • Reesink FE , LemstraAW, Van DijkKDet al. CSF alpha-synuclein does not discriminate dementia with Lewy bodies from Alzheimer’s disease. J. Alzheimers Dis.22(1), 87–95 (2010).
  • Aerts MB , EsselinkRA, AbdoWF, BloemBR, VerbeekMM. CSF alpha-synuclein does not differentiate between parkinsonian disorders. Neurobiol. Aging33(2), 430.e1–e3 (2012).
  • Park MJ , CheonSM, BaeHR, KimSH, KimJW. Elevated levels of alpha-synuclein oligomer in the cerebrospinal fluid of drug-naive patients with Parkinson’s disease. J. Clin. Neurol.7(4), 215–222 (2011).
  • Aasly JO , JohansenKK, BronstadGet al. Elevated levels of cerebrospinal fluid alpha-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers. Front. Aging Neurosci.6, 248 (2014).
  • Tinsley RB , KotschetK, ModestoDet al. Sensitive and specific detection of alpha-synuclein in human plasma. J. Neurosci. Res.88(12), 2693–2700 (2010).
  • Duran R , BarreroFJ, MoralesB, LunaJD, RamirezM, VivesF. Plasma alpha-synuclein in patients with Parkinson’s disease with and without treatment. Mov. Disord.25(4), 489–493 (2010).
  • Tateno F , SakakibaraR, KawaiT, KishiM, MuranoT. Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease. Alzheimer Dis. Assoc. Disord.26(3), 213–216 (2012).
  • Brighina L , PrigioneA, BegniBet al. Lymphomonocyte alpha-synuclein levels in aging and in Parkinson disease. Neurobiol. Aging.31(5), 884–885 (2010).
  • Su E , BellMJ, WisniewskiSRet al. alpha-Synuclein levels are elevated in cerebrospinal fluid following traumatic brain injury in infants and children: the effect of therapeutic hypothermia. Dev. Neurosci.32(5–6), 385–395 (2010).
  • Laske C , FallgatterAJ, StranskyE, HagenK, BergD, MaetzlerW. Decreased alpha-synuclein serum levels in patients with Lewy body dementia compared with Alzheimer’s disease patients and control subjects. Dement. Geriatr. Cogn. Disord.31(6), 413–416 (2011).
  • Wennstrom M , SurovaY, HallSet al. Low CSF levels of both alpha-synuclein and the alpha-synuclein cleaving enzyme neurosin in patients with synucleinopathy. PLoS ONE8(1), e53250 (2013).
  • Wang H , WangK, XuWet al. Cerebrospinal fluid alpha-synuclein levels are elevated in multiple sclerosis and neuromyelitis optica patients during replase. J. Neurochem.122(1), 19–23 (2012).
  • Bidinosti M , ShimshekDR, MollenhauerBet al. Novel one-step immunoassays to quantify alpha-synuclein: applications for biomarker development and high-throughput screening. J. Biol. Chem.287(40), 33691–33705 (2012).
  • Emmanouilidou E , ElenisD, PapasilekasTet al. Assessment of alpha-synuclein secretion in mouse and human brain parenchyma. PLoS ONE6(7), e22225 (2011).
  • Lee HJ , BaeEJ, JangAet al. Enzyme-linked immunosorbent assays for alpha-synuclein with species and multimeric state specificities. J. Neurosci. Methods199(2), 249–257 (2011).
  • Kovacs GG , WagnerU, DumontBet al. An antibody with high reactivity for disease-associated alpha-synuclein reveals extensive brain pathology. Acta Neuropathol.124(1), 37–50 (2012).
  • Ohrfelt A , GrognetP, AndreasenNet al. Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss? Neurosci. Lett. 450(3), 332–335 (2009).
  • Kruse N , VanmechelenE, SchlossmacherMGet al. Sensitive multiplex quantification of alpha-Synuclein, DJ-1, beta-Amyloid 1–42 and Tau protein in human biological fluids based on chemiluminescence detection. Neurodegener. Dis.11(Suppl. 1) (2013).
  • Kruse N , Schulz-SchaefferWJ, SchlossmacherMG, MollenhauerB. Development of electrochemiluminescence-based singleplex and multiplex assays for the quantification of alpha-synuclein and other proteins in cerebrospinal fluid. Methods56(4), 514–518 (2012).
  • Kasuga K , TokutakeT, IshikawaAet al. Differential levels of alpha-synuclein, beta-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry81(6), 608–610 (2010).
  • Hong Z , ShiM, ChungKAet al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain133(Pt 3), 713–726 (2010).
  • Mollenhauer B , TrautmannE, TaylorPet al. Total CSF alpha-synuclein is lower in de novo Parkinson patients than in healthy subjects. Neurosci. Lett.532, 44–48 (2013).
  • Mollenhauer B , LocascioJJ, Schulz-SchaefferW, Sixel-DoringF, TrenkwalderC, SchlossmacherMG. alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol.10(3), 230–240 (2011).
  • Korff A , LiuC, GinghinaC, ShiM, ZhangJ. Alzheimer’s Disease Neuroimaging I. alpha-Synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J. Alzheimers Dis.36(4), 679–688 (2013).
  • Toledo JB , KorffA, ShawLM, TrojanowskiJQ, ZhangJ. CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and Abeta in Alzheimer’s disease. Acta Neuropathol.126(5), 683–697 (2013).
  • Hall S , OhrfeltA, ConstantinescuRet al. Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or Parkinsonian disorders. Arch. Neurol.69(11), 1445–1452 (2012).
  • Slaets S , VanmechelenE, Le BastardNet al. Increased CSF alpha-synuclein levels in Alzheimer’s disease: correlation with tau levels. Alzheimers Dement.10(5, Suppl.), S290–S298 (2014).
  • Kang JH , IrwinDJ, Chen-PlotkinASet al. Association of cerebrospinal fluid beta-amyloid 1–42, T-tau, P-tau181, and alpha-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA neurol.70(10), 1277–1287 (2013).
  • Mondello S , ConstantinescuR, ZetterbergH, AndreassonU, HolmbergB, JerominA. CSF alpha-synuclein and UCH-L1 levels in Parkinson’s disease and atypical parkinsonian disorders. Parkinsonism. Relat. Disord.20(4), 382–387 (2014).
  • El-Agnaf OM , IrvineGB. Review: formation and properties of amyloid-like fibrils derived from alpha-synuclein and related proteins. J. Struct. Biol.130(2–3), 300–309 (2000).
  • Sharon R , Bar-JosephI, FroschMP, WalshDM, HamiltonJA, SelkoeDJ. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson’s disease. Neuron37(4), 583–595 (2003).
  • Paleologou KE , KraghCL, MannDMet al. Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies. Brain132(Pt 4), 1093–1101 (2009).
  • Klucken J , OuteiroTF, NguyenP, McleanPJ, HymanBT. Detection of novel intracellular alpha-synuclein oligomeric species by fluorescence lifetime imaging. FASEB J.20(12), 2050–2057 (2006).
  • El-Agnaf OM , SalemSA, PaleologouKEet al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J.20(3), 419–425 (2006).
  • Fujiwara H , HasegawaM, DohmaeNet al. alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell. Biol.4(2), 160–164 (2002).
  • Anderson JP , WalkerDE, GoldsteinJMet al. Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem.281(40), 29739–29752 (2006).
  • Games D , SeubertP, RockensteinEet al. Axonopathy in an alpha-synuclein transgenic model of Lewy body disease is associated with extensive accumulation of C-terminal-truncated alpha-synuclein. Am. J. Pathol.182(3), 940–953 (2013).
  • El-Agnaf OM , WalshDM, AllsopD. Soluble oligomers for the diagnosis of neurodegenerative diseases. Lancet Neurol.2(8), 461–462 (2003).
  • Bartels T , ChoiJG, SelkoeDJ. alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature477(7362), 107–110 (2011).
  • Gorostidi A , BergarecheA, Ruiz-MartinezJet al. Alpha-synuclein levels in blood plasma from LRRK2 mutation carriers. PLoS ONE7(12), e52312 (2012).
  • Lindersson E , BeedholmR, HojrupPet al. Proteasomal inhibition by alpha-synuclein filaments and oligomers. J. Biol. Chem.279(13), 12924–12934 (2004).
  • Unterberger U , LachmannI, VoigtlanderTet al. Detection of disease-associated alpha-synuclein in the cerebrospinal fluid: a feasibility study. Clin. Neuropathol.33(5), 329–334 (2014).
  • Okochi M , WalterJ, KoyamaAet al. Constitutive phosphorylation of the Parkinson’s disease associated alpha-synuclein. J. Biol. Chem.275(1), 390–397 (2000).
  • Chen L , FeanyMB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat. Neurosci.8(5), 657–663 (2005).
  • Foulds PG , MitchellJD, ParkerAet al. Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson’s disease. FASEB J.25(12), 4127–4137 (2011).
  • Wang Y , ShiM, ChungKAet al. Phosphorylated alpha-synuclein in Parkinson’s disease. Sci. Transl. Med.4(121), 121ra120 (2012).
  • Fernandez E , Garcia-MorenoJM, Martin De PablosA, ChaconJ. May the evaluation of nitrosative stress through selective increase of 3-nitrotyrosine proteins other than nitroalbumin and dominant tyrosine-125/136 nitrosylation of serum alpha-synuclein serve for diagnosis of sporadic Parkinson’s disease?Antioxid. Redox. Signal.19(9), 912–918 (2013).
  • Chavez J , BajramiB, CopelandMet al. Development of quantitative methods to measure alpha-synuclein and related subspecies in CSF as candidate biomarkers for Parkinson’s disease progression. Neurodegener. Dis.11(Suppl. 1), (2013).
  • Van Dijk KD , BidinostiM, WeissA, RaijmakersP, BerendseHW, Van De BergWD. Reduced alpha-synuclein levels in cerebrospinal fluid in Parkinson’s disease are unrelated to clinical and imaging measures of disease severity. Eur. J. Neurol.21(3), 388–394 (2014).
  • Blennow K , WallinA, HagerO. Low frequency of post-lumbar puncture headache in demented patients. Acta Neurol. Scand.88(3), 221–223 (1993).
  • Braak H , Del TrediciK, RubU, De VosRA, Jansen SteurEN, BraakE. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging24(2), 197–211 (2003).
  • Barbour R , KlingK, AndersonJPet al. Red blood cells are the major source of alpha-synuclein in blood. Neurodegener. Dis.5(2), 55–59 (2008).
  • Scherzer CR , GrassJA, LiaoZet al. GATA transcription factors directly regulate the Parkinson’s disease-linked gene alpha-synuclein. Proc. Natl Acad. Sci. USA105(31), 10907–10912 (2008).
  • Mollenhauer B , TrautmannE, OtteBet al. alpha-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system. J. Neural. Transm.119(7), 739–746 (2012).
  • Mata IF , ShiM, AgarwalPet al. SNCA variant associated with Parkinson disease and plasma alpha-synuclein level. Arch. Neurol.67(11), 1350–1356 (2010).
  • Besong-Agbo D , WolfE, JessenFet al. Naturally occurring alpha-synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology80(2), 169–175 (2013).
  • Devic I , HwangH, EdgarJSet al. Salivary alpha-synuclein and DJ-1: potential biomarkers for Parkinson’s disease. Brain134(Pt 7), e178 (2011).
  • Bolstad N , WarrenDJ, NustadK. Heterophilic antibody interference in immunometric assays. Best Pract. Res. Clin. Endocrinol. Metab.27(5), 647–661 (2013).
  • Sehlin D , SollvanderS, PaulieSet al. Interference from heterophilic antibodies in amyloid-beta oligomer ELISAs. J. Alzheimers Dis.21(4), 1295–1301 (2010).
  • Bruggink KA , KuiperijHB, Ekholm-PetterssonF, VerbeekMM. Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease. Neurology77(5), 510 ; author reply 510–511 (2011).
  • Kasuga K , NishizawaM, IkeuchiT. alpha-synuclein as CSF and blood biomarker of dementia with Lewy bodies. Int. J. Alzheimers Dis.2012, 437025 (2012).
  • Kapaki E , ParaskevasGP, EmmanouilidouE, VekrellisK. The diagnostic value of CSF alpha-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer’s disease. PLoS ONE8(11), e81654 (2013).
  • Teunissen CE , TumaniH, BennettJLet al. Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker studies. Mult. Scler. Int.2011, 246412 (2011).
  • Vakharia VN , LoteH. Introduction of Sprotte needles to a single-centre acute neurology service: before and after study. JRSM Short Rep.3(12), 82 (2012).
  • Del Campo M , MollenhauerB, BertolottoAet al. Recommendations to standardize preanalytical confounding factors in Alzheimer’s and Parkinson’s disease cerebrospinal fluid biomarkers: an update. Biomark. Med.6(4), 419–430 (2012).
  • Noguchi-Shinohara M , TokudaT, YoshitaMet al. CSF alpha-synuclein levels in dementia with Lewy bodies and Alzheimer’s disease. Brain Res.1251, 1–6 (2009).
  • Mignini F , BronzettiE, FeliciLet al. Dopamine receptor immunohistochemistry in the rat choroid plexus. J. Auton. Pharmacol.20(5–6), 325–332 (2000).
  • Wennstrom M , LondosE, MinthonL, NielsenHM. Altered CSF orexin and alpha-synuclein levels in dementia patients. J. Alzheimers. Dis.29(1), 125–132 (2012).
  • Kang JE , LimMM, BatemanRJet al. Amyloid-beta dynamics are regulated by orexin and the sleep–wake cycle. Science326(5955), 1005–1007 (2009).
  • Bateman RJ , WenG, MorrisJC, HoltzmanDM. Fluctuations of CSF amyloid-beta levels: implications for a diagnostic and therapeutic biomarker. Neurology68(9), 666–669 (2007).
  • Spies PE , SlatsD, RikkertMG, TsengJ, ClaassenJA, VerbeekMM. CSF alpha-synuclein concentrations do not fluctuate over hours and are not correlated to amyloid beta in humans. Neurosci. Lett.504(3), 336–338 (2011).
  • Spies PE , MelisRJ, SjogrenMJ, RikkertMG, VerbeekMM. Cerebrospinal fluid alpha-synuclein does not discriminate between dementia disorders. J. Alzheimers Dis.16(2), 363–369 (2009).
  • Shi M , BradnerJ, HancockAMet al. Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann. Neurol.69(3), 570–580 (2011).
  • Herbert MK , AertsMB, BeenesMet al. CSF neurofilament light chain but not FLT3 ligand discriminates Parkinsonian disorders. Front Neurol.6, 91 (2015).
  • Abdo WF , BloemBR, Van GeelWJ, EsselinkRA, VerbeekMM. CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson’s disease. Neurobiol. Aging28(5), 742–747 (2007).
  • Giasson BI , FormanMS, HiguchiMet al. Initiation and synergistic fibrillization of tau and alpha-synuclein. Science300(5619), 636–640 (2003).
  • Shi M , FurayAR, SossiVet al. DJ-1 and alphaSYN in LRRK2 CSF do not correlate with striatal dopaminergic function. Neurobiol. Aging33(4), 836e835–e837 (2012).
  • Mollenhauer B , TrautmannE, Sixel-DoringFet al. Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology81(14), 1226–1234 (2013).
  • Parkinson Progression Marker I . The Parkinson Progression Marker Initiative (PPMI). Prog. Neurobiol.95(4), 629–635 (2011).
  • Jellinger KA , AttemsJ. Neuropathological evaluation of mixed dementia. J. Neurol. Sci257(1–2), 80–87 (2007).
  • Slaets S , Le BastardN, TheunsJet al. Amyloid pathology influences abeta1–42 cerebrospinal fluid levels in dementia with lewy bodies. J. Alzheimers Dis.35(1), 137–146 (2013).
  • Parnetti L , CastriotoA, ChiasseriniDet al. Cerebrospinal fluid biomarkers in Parkinson disease. Nat. Rev. Neurol.9(3), 131–140 (2013).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.