A comparison between tau and amyloid‐b cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease

Katherine W Turk,Brigid Dwyer,Jonathan D Cherry,Jesse Mez,Michael L Alosco,Victor E Alvarez,Thor D Stein,Douglas I Katz,Lee E Goldstein,Ann C Mckee,Bertrand R Huber,Neil W Kowall,Weiming Xia,Yorghos Tripodis,Raymond Nicks ,Guowang Meng ,Andrew E Budson ,Robert Stern ,Alexandra Geada ,Robert C Cantu

doi:10.1002/alz.051392

Abstract

AbstractBackgroundCerebrospinal 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.MethodA 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 (Ab1‐40, Ab1‐42), total tau (t‐tau), and phosphorylated tau (p‐tau181 and p‐tau231).ResultThe low CTE group had higher levels of p‐tau231 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 Aβ1‐42 compared to no CTE/no AD (p=0.016). The high CTE group had higher levels of p‐tau231 compared to AD (p=0.025) and lower levels of Aβ1‐42 compared to the AD group (p=0.015). Importantly, p‐tau231 and Aβ1‐42 were predictors of diagnosis of CTE vs. no CTE/no AD and CTE vs. AD (Figure 1).ConclusionIncreased CSF p‐tau231 is a promising potentially sensitive biomarkers of CTE and decreased CSF Aβ1‐42 in CTE warrants further investigation as to underlying mechanism and potential as an additional CTE biomarker.

Highlights

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
192 participants with post-mortem CSF available were enrolled from three study groups. 100 donated their brains to the Veteran’s Affairs-Boston University-Concussion Legacy Foundation Brain Bank (VA-BU-CLF) as part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) study, 38 were donated to the Framingham Heart Study (FHS), and 54 were donated to Boston University’s Alzheimer’s Disease Research Center (ADRC) as part of the Health Outreach Program for the Elderly study
As CTE is defined pathologically by abnormally phosphorylated tau accumulation within neurons, astrocytes, and cell processes [7], increased p-tau231 may be due to tau leakage from cells into the CSF, which may be present even relatively early on in the disease course when clinical symptoms are relatively mild. p-tau231 was significantly increased in both low and high stage CTE groups compared to AD groups, which could reflect increased neuron and axonal damage in CTE

Summary

Introduction

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. Chronic Traumatic Encephalopathy (CTE) and Alzheimer disease (AD) are neurodegenerative conditions causing memory loss that can only be definitively diagnosed by pathologic examination While both disease processes involve considerable tau protein deposition, amyloid-β plaque formation is considered a prominent feature only in AD. Prior studies of Aβ deposition in CTE [5] led us to hypothesize that CSF Aβ1 − 40 would be decreased in cases with co-occurring CTE and AD compared to non-AD/ non-CTE cases, representing a potential interaction between AD and CTE. To test these hypotheses, we measured CSF levels of Aβ1 − 40 , Aβ42, t-tau, p-tau181 and p-tau231

Methods

Discussion

Conclusion