A comparison between tau and amyloid-β cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease

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 (Aβ_1-40, Aβ_1-42)_, total tau (t-tau), and phosphorylated tau (p-tau₁₈₁ and p-tau₂₃₁). CSF analytes were then compared across the pathological groups: no CTE/no AD (control), Low CTE, Low AD, High CTE, Intermediate/High AD, and AD+CTE. Results: Among the Low disease state groups, the Low CTE group had significantly higher levels of p-tau₂₃₁ versus the control group and compared to the Low AD group. The Low CTE group was also found to have significantly lower levels of Aβ_1-42 compared to the control group. The high CTE group had higher levels of p-tau₂₃₁ and lower levels of Aβ_1-42 compared to Intermediate/High AD group. Conclusions: Importantly, p-tau₂₃₁ and Aβ_1-42 were predictors of diagnosis of CTE vs. control and CTE vs. AD. Increased CSF p-tau₂₃₁ is a promising potentially sensitive biomarker of CTE, and CSF Aβ_1-42 needs further investigation in CTE.