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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 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 Aβ1-42 compared to the control group. The high CTE group had higher levels of p-tau231 and lower levels of Aβ1-42 compared to Intermediate/High AD group. Conclusions Importantly, p-tau231 and Aβ1-42 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 Aβ1-42 needs further investigation in CTE.

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.

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. Method: A total of 192 participants from the Boston University AD Center and VA-BU-CLF Center had post-mortem CSF collected at autopsy. Participants were divided into pathological groups based on consensus AD and CTE criteria, resulting in 61 participants with CTE (18 low, 43 high stage), 79 participants with AD (23 low, 56 intermediate to high pathological change), 11 participants with concurrent CTE and AD, and 41 participants lacking both CTE and AD neuropathology. The Meso Scale Discovery immunoassay system was utilized to measure amyloid-beta (Ab 1-40, Ab 1-42 ) , total tau (t-tau), and phosphorylated tau (p-tau 181 and p-tau 231 ).Result: The low CTE group had higher levels of p-tau 231 compared no CTE/no AD (p=0.041), and compared to the low AD group (p=0.018). The low CTE group had lower levels of Aβ 1-42 compared to no CTE/no AD (p=0.016). The high CTE group had higher levels of p-tau 231 compared to AD (p=0.025) and lower levels of Aβ 1-42 compared to the AD group (p=0.015). Importantly, p-tau 231 and Aβ 1-42 were predictors of diagnosis of CTE vs. no CTE/no AD and CTE vs. AD (Figure 1). Conclusion:Increased CSF p-tau 231 is a promising potentially sensitive biomarkers of CTE and decreased CSF Aβ 1-42 in CTE warrants further investigation as to underlying mechanism and potential as an additional CTE biomarker.

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