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BMC Neurology
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Research article

Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer’s disease, mild cognitive impairment, or healthy controls: a two year follow-up study

Authors: Guro Berge, Sigrid B. Sando, Grethe Albrektsen, Camilla Lauridsen, Ina Møller, Gøril R. Grøntvedt, Geir Bråthen, Linda R. White

Published in: BMC Neurology | Issue 1/2016

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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.

Conclusion

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.
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Metadata
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
Authors
Guro Berge
Sigrid B. Sando
Grethe Albrektsen
Camilla Lauridsen
Ina Møller
Gøril R. Grøntvedt
Geir Bråthen
Linda R. White
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0706-0

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