title: Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer's disease, mild cognitive impairment, or healthy controls: a two year follow-up study.
abstract: BACKGROUND
  α-Synuclein has been proposed as a potential biomarker for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, results from α-synuclein measurements in cerebrospinal fluid (CSF) have been inconclusive, and to our knowledge, longitudinal studies of changes prior to the AD diagnosis have not been investigated.
  
  
  METHODS
  Levels of α-synuclein at baseline and after one and two years were measured in CSF, by enzyme-linked immunosorbent assay. Twenty-six patients with early AD (AD-AD), 48 patients with aMCI, subdivided as 23 that developed AD during follow-up (MCI-AD), and 25 that did not (MCI-MCI), and 25 healthy control individuals, were included. One-way ANOVA was applied to compare mean α-synuclein baseline values between all four study groups, and a linear mixed model was used to compare mean change over time between the three patient groups. Linear associations between α-synuclein and amyloid-β 1-42 (Aβ42), amyloid-β 1-40 (Aβ40), total tau and phosphorylated tau were also examined.
  
  
  RESULTS
  A large variation in individual α-synuclein CSF levels was observed, particularly in the MCI-AD group. No significant differences were found in mean α-synuclein levels between all the study groups at baseline. When using a linear mixed model, no significant differences were found at follow-up for estimated mean changes between the patient groups. MCI-AD patients with short duration of symptoms prior to inclusion in the study (≤2 years) had considerably higher mean CSF α-synuclein levels compared to patients with a longer symptom duration (802.2 vs. 442.8 pg/mL, p = 0.01). No such difference was seen in the MCI-MCI or AD-AD groups. Significant linear associations (p < 0.0005) between α-synuclein and Aβ40, total tau and phosphorylated tau were found.
  
  
  CONCLUSIONS
  The observed difference in mean CSF α-synuclein level according to duration of symptoms in the MCI-AD group, may be an indication of changes related to disease progression. However, the lack of significant differences between groups, as well as the large individual variation in CSF levels of α-synuclein in the present study, suggest that α-synuclein is not a useful biomarker for AD.
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, NO, 7491, Norway.
authors.forename: Guro
authors.initials: G
authors.lastname: Berge
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, NO, 7491, Norway.|Department of Neurology, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Sigrid B
authors.initials: SB
authors.lastname: Sando
authors.affiliation: Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Grethe
authors.initials: G
authors.lastname: Albrektsen
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, NO, 7491, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Lauridsen
authors.affiliation: Department of Neurology, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Ina
authors.initials: I
authors.lastname: Møller
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, NO, 7491, Norway.|Department of Neurology, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Gøril R
authors.initials: GR
authors.lastname: Grøntvedt
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, NO, 7491, Norway.|Department of Neurology, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Bråthen
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, NO, 7491, Norway. linda.white@ntnu.no.|Department of Neurology, University Hospital of Trondheim, Trondheim, Norway. linda.white@ntnu.no.
authors.forename: Linda R
authors.initials: LR
authors.lastname: White
keywords: Biomarker; Dementia; ELISA; Longitudinal