Increased CSF α-synuclein levels in Alzheimer's disease: correlation with tau levels.
BACKGROUND
Given the difficult clinical differential diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), growing interest resulted in research on α-synuclein as a potential cerebrospinal fluid biomarker (CSF) for synucleinopathies.


METHODS
CSF α-synuclein-140 concentrations were determined by a prototype xMAP™ bead-based assay (Innogenetics NV, Belgium). In addition, CSF amyloid β1-42 (Aβ1-42), total tau (T-tau), and phosphorylated tau (P-tau181P) levels were determined.


RESULTS
CSF α-synuclein levels were higher in AD patients as compared with cognitively healthy controls (P=.019) and patients with synucleinopathies (P<.001). CSF α-synuclein levels were correlated with T-tau (P<.001) and P-tau181P (P<.001) levels in autopsy-confirmed AD patients. A diagnostic algorithm using α-synuclein and P-tau181P discriminated neuropathologically confirmed AD from DLB patients, resulting in sensitivity and specificity values of 85% and 81%, respectively.


CONCLUSIONS
Because CSF α-synuclein levels were significantly higher in AD as compared with synucleinopathies, α-synuclein might have a value as a biomarker for differential dementia diagnosis.
Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Sylvie
S
Slaets
Innogenetics NV (Miraca/Fujirebio Group), Ghent, Belgium.
Eugeen
E
Vanmechelen
Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Nathalie
N
Le Bastard
Innogenetics NV (Miraca/Fujirebio Group), Ghent, Belgium.
Hilde
H
Decraemer
Innogenetics NV (Miraca/Fujirebio Group), Ghent, Belgium.
Manu
M
Vandijck
Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Jean-Jacques
JJ
Martin
Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Peter Paul
PP
De Deyn
Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium. Electronic address: sebastiaan.engelborghs@uantwerpen.be.
Sebastiaan
S
Engelborghs
D000368:Aged; D000465:Algorithms; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C497604:SNCA protein, human; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Alzheimer's disease; Biomarker; Cerebrospinal fluid; Dementia; Dementia with Lewy bodies; tau; α-Synuclein