ALZHEIMER disease blood biomarkers may be less accurate in veterans with prior traumatic brain injury.
Alzheimer Disease Blood Biomarkers Show Reduced Accuracy
A history of traumatic brain injury (TBI) may reduce the diagnostic accuracy of emerging Alzheimer disease blood biomarkers, according to new findings from a cross-sectional diagnostic test study of older veterans without dementia.
The study evaluated whether plasma phosphorylated tau 217 (p-tau217)/amyloid-β 42 (Aβ42), an Alzheimer disease blood biomarker ratio used to detect amyloid positivity, performed equally well in individuals with and without prior TBI. Researchers analyzed existing data and banked plasma from 272 Vietnam War veterans enrolled between 2013 and 2020, all of whom were cognitively unimpaired or had mild cognitive impairment and had amyloid PET imaging available.
Plasma biomarker analysis took place from 2024 to 2025, with data analysis completed between July 2025 and February 2026. Participants were grouped by TBI history, including no TBI, TBI with loss of consciousness for 0 to 5 minutes, and TBI with loss of consciousness for more than 5 minutes.
TBI Severity May Modify Test Performance
Among the 272 participants, mean age was 70 years, 99.3% were male, and 30.5% were amyloid PET positive. The plasma p-tau217/Aβ42 ratio showed high accuracy in veterans without TBI, reaching 90%. However, accuracy declined to 78% in those with TBI and loss of consciousness for 0 to 5 minutes, and to 63% in those with loss of consciousness for more than 5 minutes.
The reduced performance appeared to be driven mainly by lower sensitivity, meaning the test may miss amyloid PET positive cases in individuals with TBI history. Similar patterns were observed for plasma p-tau217 alone and the plasma Aβ42/40 ratio.
Caution Needed When Interpreting Results
The findings suggest that TBI history and severity may modify the accuracy of Alzheimer disease blood biomarkers when predicting brain amyloid PET positivity. Results remained similar after excluding veterans with TBI within the previous 10 years and when amyloid PET positivity was defined using a quantitative threshold rather than consensus visual read.
Clinically, the study raises concern that the p-tau217/Aβ42 ratio may miss more than half of amyloid PET positive cases among cognitively unimpaired individuals or those with mild cognitive impairment who have a TBI history. The authors advised caution when interpreting Alzheimer disease blood biomarkers in this setting, particularly as blood based testing becomes increasingly important in diagnostic pathways.
Reference
Rosen-Lang Y et al. Prior traumatic brain injury and Alzheimer disease blood biomarkers. JAMA Neurol. 2026;10.1001/jamaneurol.2026.2042.
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