A Comparison Between Tau and Amyloid-β Cerebrospinal Fluid Biomarkers in Chronic Traumatic Encephalopathy and Alzheimer Disease

Abstract

Background Cerebrospinal fluid (CSF) tau and beta-amyloid levels in chronic traumatic encephalopathy (CTE), a disease which can be clinically indistinguishable from Alzheimer’s disease (AD), are largely unknown. We examined postmortem CSF analytes among participants with autopsy confirmed CTE and AD. Methods In this cross-sectional study 192 participants from the Boston University AD Research Center, VA-BU-CLF Center, and Framingham Heart Study (FHS) had post-mortem CSF collected at autopsy. Participants were divided into pathological groups based on AD and CTE criteria, with 61 CTE participants (18 low, 43 high stage), 79 AD participants (23 low, 56 intermediate to high), 11 participants with CTE combined with AD, and 41 participants lacking both CTE and AD neuropathology. The Meso Scale Discovery immunoassay system was utilized to measure amyloid-beta (Aβ1 − 40, Aβ1 − 42), total tau (t-tau), and phosphorylated tau (p-tau181 and p-tau231). CSF analytes were then compared across the six pathological groups: no CTE/no AD, Low CTE, Low AD, High CTE, Intermediate/High AD, and AD + CTE. Results The low CTE group had higher levels of p-tau231 compared no CTE/no AD (p < 0.001), and compared to the low AD group (p = 0.002). The low CTE group had lower levels of Aβ1−42 compared to no CTE/no AD (p = 0.009). The high CTE group had higher levels of p-tau231 compared to intermediate/high AD (p < 0.001). Conclusions Importantly, p-tau231 and Aβ1−42 were predictors of diagnosis of CTE vs. no CTE/no AD and CTE vs. AD. Increased CSF p-tau231 is a promising potentially sensitive biomarker of CTE, and CSF Aβ1−42 needs further investigation in CTE.