Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer’s disease and other neurodegenerative diseases

References

• Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science. 2016;353(6301):777–783.
   PubMed Web of Science ®Google Scholar
• Andreasson KI, Bachstetter AD, Colonna M, et al. Targeting innate immunity for neurodegenerative disorders of the central nervous system. J Neurochem. 2016;138(5):653–693.
   PubMed Web of Science ®Google Scholar
• Scheltens P, Blennow K, Breteler MMB, et al. Alzheimer’s disease. Lancet. 2016;388:505–517.
   PubMed Web of Science ®Google Scholar
• Hardy J. The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal. J Neurochem. 2009;110(4):1129–1134.
   PubMed Web of Science ®Google Scholar
• Hashimoto M, Rockenstein E, Crews L, et al. Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases. Neuromolecular Med. 2003;4(1–2):21–36.
   PubMed Web of Science ®Google Scholar
• Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8(1):1–13.
   PubMed Web of Science ®Google Scholar
• Johnson LV, Leitner WP, Rivest AJ, et al. The Alzheimer’s A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci U S A. 2002;99(18):11830–11835.
   PubMed Web of Science ®Google Scholar
• Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405.
   PubMed Web of Science ®Google Scholar
• Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16(6):358–372.
   PubMed Web of Science ®Google Scholar
• Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14(7):463–477.
   PubMed Web of Science ®Google Scholar
• Glass CK, Saijo K, Winner B, et al. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140(6):918–934.
   PubMed Web of Science ®Google Scholar
• Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement. 2016;12(6):719–732.
   PubMed Web of Science ®Google Scholar
• Minter MR, Taylor JM, Crack PJ. The contribution of neuroinflammation to amyloid toxicity in Alzheimer’s disease. J Neurochem. 2016;136(3):457–474.
   PubMed Web of Science ®Google Scholar
• Wyss-Coray T, Rogers J. Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med. 2012;2(1):a006346.
   PubMed Web of Science ®Google Scholar
• Mosher KI, Wyss-Coray T. Microglial dysfunction in brain aging and Alzheimer’s disease. Biochem Pharmacol. 2014;88(4):594–604.
   PubMed Web of Science ®Google Scholar
• Bettens K, Sleegers K, van Broeckhoven C. Genetic insights in Alzheimer’s disease. Lancet Neurol. 2013;12(1):92–104.
   PubMed Web of Science ®Google Scholar
• van Cauwenberghe C, van Broeckhoven C, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med. 2016;18(5):421–430.
   PubMed Web of Science ®Google Scholar
• Perry VH, Teeling J. Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Semin Immunopathol. 2013;35(5):601–612.
   PubMed Web of Science ®Google Scholar
• Li C, Zhao R, Gao K, et al. Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer’s disease. Curr Alzheimer Res. 2011;8(1):67–80.
   PubMed Web of Science ®Google Scholar
• Veerhuis R, Nielsen HM, Tenner AJ. Complement in the brain. Mol Immunol. 2011;48(14):1592–1603.
   PubMed Web of Science ®Google Scholar
• Ishizuka K, Kimura T, Igata-Yi R, et al. Identification of monocyte chemoattractant protein-1 in senile plaques and reactive microglia of Alzheimer’s disease. Psychiatry Clin Neurosci. 1997;51(3):135–138.
   PubMed Web of Science ®Google Scholar
• Tarkowski E, Andreasen N, Tarkowski A, et al. Intrathecal inflammation precedes development of Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003;74(9):1200–1205.
   PubMed Web of Science ®Google Scholar
• Burguillos MA, Deierborg T, Kavanagh E, et al. Caspase signalling controls microglia activation and neurotoxicity. Nature. 2011;472(7343):319–324.
   PubMed Web of Science ®Google Scholar
• Vodovotz Y, Lucia MS, Flanders KC, et al. Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer’s disease. J Exp Med. 1996;184(4):1425–1433.
   PubMed Web of Science ®Google Scholar
• Okello A, Edison P, Archer HA, et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology. 2009;72(1):56–62.
   PubMed Web of Science ®Google Scholar
• Wiley CA, Lopresti BJ, Venneti S, et al. Carbon 11-labeled Pittsburgh compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol. 2009;66(1):60–67.
   PubMedGoogle Scholar
• Varley J, Brooks DJ, Edison P. Imaging neuroinflammation in Alzheimer’s disease and other dementias: recent advances and future directions. Alzheimers Dement. 2015;11(9):1110–1120.
   PubMed Web of Science ®Google Scholar
• Edison P, Archer HA, Gerhard A, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32(3):412–419.
   PubMed Web of Science ®Google Scholar
• Rayaprolu S, Mullen B, Baker M, et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease. Mol Neurodegener. 2013;8:19.
   PubMed Web of Science ®Google Scholar
• Noyce AJ, Bestwick JP, Silveira-Moriyama L, et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol. 2012;72(6):893–901.
   PubMed Web of Science ®Google Scholar
• Gerhard A. TSPO imaging in parkinsonian disorders. Clin Transl Imaging. 2016;4:183–190.
   PubMed Web of Science ®Google Scholar
• Crotti A, Glass CK. The choreography of neuroinflammation in Huntington’s disease. Trends Immunol. 2015;36(6):364–373.
   PubMed Web of Science ®Google Scholar
• Corcia P, Tauber C, Vercoullie J, et al. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One. 2012;7(12):e52941.
   PubMed Web of Science ®Google Scholar
• Zhang J. Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging. J Neuroinflammation. 2015;12:108.
   PubMed Web of Science ®Google Scholar
• Craig-Schapiro R, Perrin RJ, Roe CM, et al. YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry. 2010;68(10):903–912.
   PubMed Web of Science ®Google Scholar
• Rehli M, Krause SW, Andreesen R. Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics. 1997;43(2):221–225.
   PubMed Web of Science ®Google Scholar
• Hauschka PV, Mann KG, Price P, et al. Report of the Ad Hoc committee on nomenclature and standards for bone proteins and growth factors. J Bone Miner Res. 1986;1(5):485–486.
   PubMed Web of Science ®Google Scholar
• Rathcke CN, Vestergaard H. YKL-40–an emerging biomarker in cardiovascular disease and diabetes. Cardiovasc Diabetol. 2009;8:61.
   PubMed Web of Science ®Google Scholar
• Johansen JS, Jensen BV, Roslind A, et al. Serum YKL-40, a new prognostic biomarker in cancer patients? Cancer Epidemiol Biomark Prev. 2006;15(2):194–202.
   PubMed Web of Science ®Google Scholar
• Henrissat B, Bairoch A. New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J. 1993;293(3):781–788.
   PubMed Web of Science ®Google Scholar
• Prakash M, Bodas M, Prakash D, et al. Diverse pathological implications of YKL-40: answers may lie in “outside-in” signaling. Cell Signal. 2013;25(7):1567–1573.
   PubMed Web of Science ®Google Scholar
• Lee CG, Da Silva CA, Dela Cruz CS, et al. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu Rev Physiol. 2011;73:479–501.
   PubMed Web of Science ®Google Scholar
• Malinda KM, Ponce L, Kleinman HK, et al. Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells. Exp Cell Res. 1999;250(1):168–173.
   PubMed Web of Science ®Google Scholar
• Fusetti F, Pijning T, Kalk KH, et al. Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39. J Biol Chem. 2003;278(39):37753–37760.
   PubMed Web of Science ®Google Scholar
• Rehli M, Niller -H-H, Ammon C, et al. Transcriptional regulation of CHI3L1, a marker gene for late stages of macrophage differentiation. J Biol Chem. 2003;278(45):44058–44067.
   PubMed Web of Science ®Google Scholar
• Johansen JS, Jensen BV, Roslind A, et al. Is YKL-40 a new therapeutic target in cancer? Expert Opin Ther Targets. 2007;11(2):219–234.
   PubMed Web of Science ®Google Scholar
• Bonneh-Barkay D, Wang G, Starkey A, et al. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. J Neuroinflammation. 2010;7:34.
   PubMed Web of Science ®Google Scholar
• Bonneh-Barkay D, Bissel SJ, Kofler J, et al. Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. Brain Pathol. 2012;22(4):530–546.
   PubMed Web of Science ®Google Scholar
• Olsson B, Hertze J, Lautner R, et al. Microglial markers are elevated in the prodromal phase of Alzheimer’s disease and vascular dementia. J Alzheimers Dis. 2013;33(1):45–53.
   PubMed Web of Science ®Google Scholar
• Hjalmarsson C, Bjerke M, Andersson B, et al. Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with acute ischemic stroke. J Cent Nerv Syst Dis. 2014;6:51–58.
   PubMedGoogle Scholar
• Park HY, Jun C-D, Jeon S-J, et al. Serum YKL-40 levels correlate with infarct volume, stroke severity, and functional outcome in acute ischemic stroke patients. PLoS One. 2012;7(12):e51722.
   PubMed Web of Science ®Google Scholar
• Rathcke CN, Thomsen SB, Linneberg A, et al. Variations of CHI3L1, levels of the encoded glycoprotein YKL-40 and prediction of fatal and non-fatal ischemic stroke. PLoS One. 2012;7(8):e43498.
   PubMed Web of Science ®Google Scholar
• Kjaergaard AD, Johansen JS, Bojesen SE, et al. Elevated plasma YKL-40, lipids and lipoproteins, and ischemic vascular disease in the general population. Stroke J Cereb Circ. 2015;46(2):329–335.
   Web of Science ®Google Scholar
• Malmeström C, Axelsson M, Lycke J, et al. CSF levels of YKL-40 are increased in MS and replaces with immunosuppressive treatment. J Neuroimmunol. 2014;269(1–2):87–89.
   PubMed Web of Science ®Google Scholar
• Martínez MAM, Olsson B, Bau L, et al. Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis. Mult Scler. 2015;21(5):550–561.
   PubMed Web of Science ®Google Scholar
• Burman J, Raininko R, Blennow K, et al. YKL-40 is a CSF biomarker of intrathecal inflammation in secondary progressive multiple sclerosis. J Neuroimmunol. 2016;292:52–57.
   PubMed Web of Science ®Google Scholar
• Hinsinger G, Galéotti N, Nabholz N, et al. Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis. Mult Scler. 2015;21(10):1251–1261.
   PubMed Web of Science ®Google Scholar
• Matute-Blanch C, Río J, Villar LM, et al. Chitinase 3-like 1 is associated with the response to interferon-beta treatment in multiple sclerosis. J Neuroimmunol. 2017;303:62–65.
   PubMed Web of Science ®Google Scholar
• Cantó E, Tintoré M, Villar LM, et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain. 2015;138(Pt 4):918–931.
   PubMed Web of Science ®Google Scholar
• Comabella M, Fernández M, Martin R, et al. Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain. 2010;133(Pt 4):1082–1093.
   PubMed Web of Science ®Google Scholar
• Mattsson N, Tabatabaei S, Johansson P, et al. Cerebrospinal fluid microglial markers in Alzheimer’s disease: elevated chitotriosidase activity but lack of diagnostic utility. Neuromolecular Med. 2011;13(2):151–159.
   PubMed Web of Science ®Google Scholar
• Alcolea D, Carmona-Iragui M, Suárez-Calvet M, et al. Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer’s disease. J Alzheimers Dis. 2014;42(1):157–167.
   PubMed Web of Science ®Google Scholar
• Hellwig K, Kvartsberg H, Portelius E, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther. 2015;7(1):74.
   PubMed Web of Science ®Google Scholar
• Janelidze S, Hertze J, Zetterberg H, et al. Cerebrospinal fluid neurogranin and YKL-40 as biomarkers of Alzheimer’s disease. Ann Clin Transl Neurol. 2016;3(1):12–20.
   PubMed Web of Science ®Google Scholar
• Kester MI, Teunissen CE, Sutphen C, et al. Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer’s disease in a memory clinic cohort. Alzheimers Res Ther. 2015;7(1):59.
   PubMed Web of Science ®Google Scholar
• Wennström M, Surova Y, Hall S, et al. The inflammatory marker YKL-40 is elevated in cerebrospinal fluid from patients with Alzheimer’s but not parkinson’s disease or dementia with lewy bodies. PLoS One. 2015;10(8):e0135458.
   PubMed Web of Science ®Google Scholar
• Olsson B, Constantinescu R, Holmberg B, et al. The glial marker YKL-40 is decreased in synucleinopathies. Mov Disord. 2013;28(13):1882–1885.
   PubMed Web of Science ®Google Scholar
• Hall S, Surova Y, Öhrfelt A, et al. Longitudinal measurements of cerebrospinal fluid biomarkers in Parkinson’s disease. Mov Disord. 2016;31(6):898–905.
   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(11):1240–1247.
   PubMed Web of Science ®Google Scholar
• Winer L, Srinivasan D, Chun S, et al. SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense oligonucleotide therapy. JAMA Neurol. 2013;70(2):201–207.
   PubMed Web of Science ®Google Scholar
• Teunissen CE, Elias N, Koel-Simmelink MJA, et al. Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics. Alzheimers Dement (Amst.). 2016;2:86–94.
   PubMedGoogle Scholar
• Vinther-Jensen T, Budtz-Jørgensen E, Simonsen AH, et al. YKL-40 in cerebrospinal fluid in Huntington’s disease–a role in pathology or a nonspecific response to inflammation? Parkinsonism Relat Disord. 2014;20(11):1301–1303.
   PubMed Web of Science ®Google Scholar
• Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–629.
   PubMed Web of Science ®Google Scholar
• Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9(11):1118–1127.
   PubMed Web of Science ®Google Scholar
• Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270–279.
   PubMed Web of Science ®Google Scholar
• McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–269.
   PubMed Web of Science ®Google Scholar
• Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–292.
   PubMed Web of Science ®Google Scholar
• McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–944.
   PubMed Web of Science ®Google Scholar
• Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004;256(3):240–246.
   PubMed Web of Science ®Google Scholar
• Xia J, Broadhurst DI, Wilson M, et al. Translational biomarker discovery in clinical metabolomics: an introductory tutorial. Metabolomics. 2013;9(2):280–299.
   PubMed Web of Science ®Google Scholar
• Choi J, Lee H-W, Suk K. Plasma level of chitinase 3-like 1 protein increases in patients with early Alzheimer’s disease. J Neurol. 2011;258(12):2181–2185.
   PubMed Web of Science ®Google Scholar
• Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673–684.
   PubMed Web of Science ®Google Scholar
• Perrin RJ, Craig-Schapiro R, Malone JP, et al. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer’s disease. PLoS One. 2011;6(1):e16032.
   PubMed Web of Science ®Google Scholar
• Rosén C, Andersson C-H, Andreasson U, et al. Increased levels of chitotriosidase and YKL-40 in cerebrospinal fluid from patients with Alzheimer’s Disease. Dement Geriatr Cogn Disord Extra. 2014;4(2):297–304.
   PubMedGoogle Scholar
• Paterson RW, Toombs J, Slattery CF, et al. Dissecting IWG-2 typical and atypical Alzheimer’s disease: insights from cerebrospinal fluid analysis. J Neurol. 2015;262(12):2722–2730.
   PubMed Web of Science ®Google Scholar
• Rodrigues FB, Byrne LM, McColgan P, et al. Cerebrospinal fluid inflammatory biomarkers reflect clinical severity in Huntington’s disease. PLoS One. 2016;11(9):e0163479.
   PubMed Web of Science ®Google Scholar
• Sutphen CL, Jasielec MS, Shah AR, et al. Longitudinal cerebrospinal fluid biomarker changes in preclinical Alzheimer disease during middle age. JAMA Neurol. 2015;72(9):1029–1042.
   PubMed Web of Science ®Google Scholar
• Antonell A, Mansilla A, Rami L, et al. Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer’s disease. J Alzheimers Dis. 2014;42(3):901–908.
   PubMed Web of Science ®Google Scholar
• Wildsmith KR, Schauer SP, Smith AM, et al. Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomics. Mol Neurodegener. 2014;9:22.
   PubMed Web of Science ®Google Scholar
• Gispert JD, Monté GC, Falcon C, et al. CSF YKL-40 and pTau181 are related to different cerebral morphometric patterns in early AD. Neurobiol Aging. 2016;38:47–55.
   PubMed Web of Science ®Google Scholar
• Alcolea D, Vilaplana E, Pegueroles J, et al. Relationship between cortical thickness and cerebrospinal fluid YKL-40 in predementia stages of Alzheimer’s disease. Neurobiol Aging. 2015;36(6):2018–2023.
   PubMed Web of Science ®Google Scholar
• Alcolea D, Martínez-Lage P, Sánchez-Juan P, et al. Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology. 2015;85(7):626–633.
   PubMed Web of Science ®Google Scholar
• Melah KE, Lu SY-F, Hoscheidt SM, et al. Cerebrospinal fluid markers of Alzheimer’s disease pathology and microglial activation are associated with altered white matter microstructure in asymptomatic adults at risk for Alzheimer’s disease. J Alzheimers Dis. 2016;50(3):873–886.
   PubMed Web of Science ®Google Scholar
• Racine AM, Koscik RL, Nicholas CR, et al. Cerebrospinal fluid ratios with Aβ42 predict preclinical brain β-amyloid accumulation. Alzheimers Dement (Amst.). 2016;2:27–38.
   PubMedGoogle Scholar
• Magdalinou N, Lees AJ, Zetterberg H. Cerebrospinal fluid biomarkers in parkinsonian conditions: an update and future directions. J Neurol Neurosurg Psychiatry. 2014;85(10):1065–1075.
   PubMed Web of Science ®Google Scholar
• McCann H, Stevens CH, Cartwright H, et al. α-Synucleinopathy phenotypes. Parkinsonism Relat Disord. 2014;20(Suppl 1):S62–67.
   PubMedGoogle Scholar
• Reitz C. Toward precision medicine in Alzheimer’s disease. Ann Transl Med. 2016;4(6):107.
   PubMed Web of Science ®Google Scholar
• Baldacci F, Lista S, Garaci F, et al. Biomarker-guided classification scheme of neurodegenerative diseases. J Sport Health Sci. 2016;5(4):383–387.
   PubMed Web of Science ®Google Scholar
• Lista S, Hampel H. Synaptic degeneration and neurogranin in the pathophysiology of Alzheimer’s disease. Expert Rev Neurother. 2016;17(1):47–57.
   PubMed Web of Science ®Google Scholar
• Morenas-Rodríguez E, Cervera-Carles L, Vilaplana E, et al. Progranulin protein levels in cerebrospinal fluid in primary neurodegenerative dementias. JAD. 2016;50(2):539–546.
   Web of Science ®Google Scholar
• Schuitemaker A, van der Doef TF, Boellaard R, et al. Microglial activation in healthy aging. Neurobiol Aging. 2012;33(6):1067–1072.
   PubMed Web of Science ®Google Scholar
• Bonneh-Barkay D, Zagadailov P, Zou H, et al. YKL-40 expression in traumatic brain injury: an initial analysis. J Neurotrauma. 2010;27(7):1215–1223.
   PubMed Web of Science ®Google Scholar
• Pasinetti GM. From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer’s disease: the role of NSAIDs and cyclooxygenase in beta-amyloidosis and clinical dementia. J Alzheimers Dis. 2002;4(5):435–445.
   PubMed Web of Science ®Google Scholar
• Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. BMJ. 2003;327(7407):128.
   PubMed Web of Science ®Google Scholar
• Hoozemans JJM, Veerhuis R, Rozemuller AJM, et al. Non-steroidal anti-inflammatory drugs and cyclooxygenase in Alzheimer’s disease. Curr Drug Targets. 2003;4(6):461–468.
   PubMed Web of Science ®Google Scholar
• ADAPT Research Group; Martin BK, Szekely C, Szekely C, Brandt J, et al. Cognitive function over time in the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol. 2008;65(7):896–905.
   PubMedGoogle Scholar
• Breitner JC, Baker LD, Montine TJ, et al. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement. 2011;7(4):402–411.
   PubMed Web of Science ®Google Scholar
• Henningsen KM, Therkelsen SK, Johansen JS, et al. Plasma YKL-40, a new biomarker for atrial fibrillation? Europace. 2009;11(8):1032–1036.
   PubMed Web of Science ®Google Scholar
• Marott SCW, Benn M, Johansen JS, et al. YKL-40 levels and atrial fibrillation in the general population. Int J Cardiol. 2013;167(4):1354–1359.
   PubMed Web of Science ®Google Scholar
• Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care. 2004;27(3):813–823.
   PubMed Web of Science ®Google Scholar
• Ma W, Wang X, Du Y, et al. Association between human cartilage glycoprotein 39 (YKL-40) and arterial stiffness in essential hypertension. BMC Cardiovasc Disord. 2012;12:35.
   PubMed Web of Science ®Google Scholar
• Rathcke CN, Vestergaard H. YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. Inflamm Res. 2006;55(6):221–227.
   PubMed Web of Science ®Google Scholar
• Iadecola C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol. 2010;120(3):287–296.
   PubMed Web of Science ®Google Scholar
• Grammas P. Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer’s disease. J Neuroinflammation. 2011;8:26.
   PubMed Web of Science ®Google Scholar
• Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011;12(12):723–738.
   PubMed Web of Science ®Google Scholar
• Erickson MA, Banks WA. Blood-brain barrier dysfunction as a cause and consequence of Alzheimer’s disease. J Cereb Blood Flow. 2013;33(10):1500–1513.
   PubMed Web of Science ®Google Scholar
• Kalra S, Grosset DG, Benamer HTS. Differentiating vascular parkinsonism from idiopathic Parkinson’s disease: a systematic review. Mov Disord. 2010;25(2):149–156.
   PubMed Web of Science ®Google Scholar
• Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011;10(9):819–828.
   PubMed Web of Science ®Google Scholar
• Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014;88(4):640–651.
   PubMed Web of Science ®Google Scholar
• Cereda E, Barichella M, Pedrolli C, et al. Diabetes and risk of Parkinson’s disease: a systematic review and meta-analysis. Diabetes Care. 2011;34(12):2614–2623.
   PubMed Web of Science ®Google Scholar
• Giuntini M, Baldacci F, Del Prete E, et al. Diabetes is associated with postural and cognitive domains in Parkinson’s disease. Results from a single-center study. Parkinsonism Relat Disord. 2014;20(6):671–672.
   PubMed Web of Science ®Google Scholar
• Lista S, Khachaturian ZS, Rujescu D, et al. Application of systems theory in longitudinal studies on the origin and progression of Alzheimer’s disease. Methods Mol Biol. 2016;1303:49–67.
   PubMedGoogle Scholar
• Hampel H, Lista S, Khachaturian ZS. Development of biomarkers to chart all Alzheimer’s disease stages: the royal road to cutting the therapeutic Gordian Knot. Alzheimers Dement. 2012;8(4):312–336.
   PubMed Web of Science ®Google Scholar
• Hampel H, O’Bryant SE, Castrillo JI, et al. PRECISION MEDICINE - The golden gate for detection, treatment and prevention of Alzheimer’s disease. J Prev Alz Dis. 2016;3(4):243–259. DOI:10.14283/jpad.2016.112.
   PubMedGoogle Scholar
• Dubois B, Hampel H, Feldman HH, et al. Preclinical Alzheimer’s disease: definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016;12(3):292–323.
   PubMed Web of Science ®Google Scholar
• Hampel H, O’Bryant SE, Durrleman S, et al.; for the Alzheimer Precision Medicine Initiative (APMI). A precision medicine initiative for Alzheimer’s disease – The road ahead to biomarker-guided integrative disease modeling. Climacteric. 2017;20(2):107–118. doi:10.1080/13697137.2017.1287866
   PubMed Web of Science ®Google Scholar