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Prior Traumatic Brain Injury and Alzheimer Disease Blood Biomarkers
Yael Rosen-Lang1, Agathe Vrillon2,3, Shlomit Pasternak1
1Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat-Gan, Israel.
JAMA Neurology
|June 29, 2026
Summary
Traumatic brain injury (TBI) history significantly reduces the accuracy of the plasma phosphorylated tau 217 (p-tau217)/amyloid-β 42 (Aβ42) ratio test for detecting brain amyloid. This Alzheimer disease blood test may miss many positive cases in veterans with TBI.
Area of Science:
- Neurology
- Biomarker research
- Geriatric medicine
Background:
- Traumatic brain injury (TBI) is a known risk factor for dementia and affects Alzheimer disease (AD) blood biomarker levels.
- The plasma phosphorylated tau 217 (p-tau217)/amyloid-β 42 (Aβ42) ratio shows high accuracy (90%) for detecting brain amyloid in civilian populations.
Purpose of the Study:
- To assess the diagnostic accuracy of emerging Alzheimer disease (AD) blood biomarkers in veterans with and without a history of TBI.
- To compare the performance of the p-tau217/Aβ42 ratio and other AD blood biomarkers across different TBI severity groups.
Main Methods:
- A cross-sectional cohort study analyzed plasma biomarkers (p-tau217/Aβ42 ratio, p-tau217, Aβ42/40 ratio) against amyloid-PET scans in 272 Vietnam War veterans.
- Veterans were categorized into three groups: no TBI, TBI with 0-5 minutes loss of consciousness (LOC), and TBI with >5 minutes LOC.
- Data were sourced from the Alzheimer Disease Neuroimaging Initiative Department of Defense (ADNI-DOD) study (2013-2020 enrollment).
Main Results:
- The plasma p-tau217/Aβ42 ratio accuracy was high in veterans without TBI (90%) but significantly lower in those with TBI (78% for 0-5 min LOC, P=.03; 63% for >5 min LOC, P<.001).
- Similar accuracy reductions were observed for plasma p-tau217 alone and the Aβ42/40 ratio.
- These findings persisted after excluding recent TBIs or using quantitative amyloid-PET thresholds.
Conclusions:
- The diagnostic accuracy of the p-tau217/Aβ42 ratio test for detecting brain amyloid is substantially reduced in veterans with a history of TBI.
- Caution is warranted when interpreting AD blood test results in individuals with TBI, as the test may miss a significant proportion of amyloid-positive cases.
- Further research is needed to understand and potentially improve AD blood biomarker performance in TBI populations.
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