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. CONCLUSION: 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.