title: α-Synuclein in cerebrospinal fluid of Alzheimer's disease and mild cognitive impairment.
abstract: In addition to amyloid-β (Aβ) and tau, α-synuclein, best known for its role in Parkinson's disease (PD), has been suggested to be involved in cognition and pathogenesis of Alzheimer's disease (AD). We investigate the potential of α-synuclein in cerebrospinal fluid (CSF) as a biomarker of cognitive decline in AD, and its prodromal phase, mild cognitive impairment (MCI). Using an established, sensitive Luminex assay, we measured α-synuclein levels in the CSF of a cohort of close to 400 healthy control, MCI, and AD subjects obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and factored in APOE genotype in data analysis. CSF α-synuclein levels were significantly higher in the MCI (p = 0.005) and AD (p < 0.001) groups, compared to controls. However, receiver operating characteristic (ROC) curve analysis suggests that CSF α-synuclein level on its own only offered modest sensitivity (65%) and specificity (74%) as a diagnostic marker of AD, with an area under the curve (AUC) value of 0.719 for AD versus controls. The effect of APOE genotype, if any, was quite subtle. However, there was a significant correlation between α-synuclein and cognition (p = 0.001), with increased α-synuclein levels associated with decreased Mini-Mental State Exam scores. Our results support a role for α-synuclein even in MCI, the early phase of AD, in addition to being a potential contributor in MCI and AD diagnosis or monitoring of disease progression.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.
authors.forename: Ane
authors.initials: A
authors.lastname: Korff
authors.forename: Changqin
authors.initials: C
authors.lastname: Liu
authors.forename: Carmen
authors.initials: C
authors.lastname: Ginghina
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein