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 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.

Neuroimmune proteins can differentiate between tauopathies

“…Postmortem fresh frozen human brain tissue was obtained and processed from 127 individuals as previously described [ 19 ]. Additionally, 29 samples of cerebrospinal fluid (CSF) were obtained as previously described [ 11 ]. Cases were evaluated from the BU CTE Center, BU Alzheimer’s Disease Center, Framingham Heart Study, and Mayo Clinic Brain Banks.…”

Football and Dementia: Understanding the Link

“…A fluid-based biomarker with sufficient sensitivity and specificity to be of practical use for identifying CTE is essential, a combined CSF p-tau 231/ Aβ 1-42 assay has shown promise distinguishing CTE from AD but limited to postmortem samples (75). A combined assay to measure levels of tau phosphorylated at threonine 181 in plasma for use in conjunction with a plasma neurofilament light chain assay to discriminate between AD and non-AD neurodegenerative dementias, for example CTE, is under development (76,77).…”

Neuroimmune proteins can differentiate between tauopathies

“…Postmortem fresh frozen human brain tissue was obtained and processed from 127 individuals as previously described [19]. Additionally, 29 samples of cerebrospinal uid (CSF) were obtained as previously described [11]. Cases were evaluated from the BU CTE Center, BU Alzheimer's Disease Center, Framingham Heart Study, and Mayo Clinic Brain Banks.…”

“…Additionally, tauopathies can only be diagnosed after death and lack speci c diagnostic biomarkers. While the use of ptau in uids, like blood and cerebrospinal uid (CSF), has shown to be a possible marker of general neurodegenerative processes, additional biomarkers are still needed that can su ciently differentiate between tauopathies and aid antemortem diagnosis [10][11][12].…”