Prior Traumatic Brain Injury May Reduce Accuracy of Alzheimer Blood Biomarkers

Prior traumatic brain injury (TBI) may reduce the diagnostic accuracy of Alzheimer disease (AD) blood biomarkers, according to findings from a cross-sectional diagnostic test study published in JAMA Neurology. Investigators reported that the plasma phosphorylated tau217 (p-tau217)/amyloid-β 42 (Aβ42) ratio performed well in older veterans without TBI history but demonstrated significantly lower accuracy in those with prior TBI.

The study evaluated existing data and banked plasma samples from the Alzheimer Disease Neuroimaging Initiative Department of Defense study. The analysis included 272 Vietnam War veterans without dementia who had amyloid-PET imaging and concurrently collected plasma available for biomarker testing. Participants were cognitively unimpaired or had mild cognitive impairment. The mean age was 70 years, 99.3% of participants were male, and 30.5% were amyloid-PET positive.

Researchers assessed the performance of the Food and Drug Administration (FDA)–approved plasma p-tau217/Aβ42 ratio, as well as plasma p-tau217 and Aβ42/40 ratio, for detecting amyloid-PET positivity. Biomarker accuracy was compared across 3 groups: veterans without TBI, veterans with TBI and loss of consciousness for 0 to 5 minutes, and veterans with TBI and loss of consciousness for more than 5 minutes.

Biomarker Accuracy Findings

• The plasma p-tau217/Aβ42 ratio was 90% accurate in veterans without TBI history.
• Accuracy decreased to 78% among veterans with TBI and loss of consciousness for 0 to 5 minutes and to 63% among those with TBI and loss of consciousness for more than 5 minutes.
• Similar patterns were observed for plasma p-tau217 alone and the plasma Aβ42/40 ratio.
• The lower performance in TBI-exposed groups was driven primarily by reduced sensitivity and a higher proportion of false-negative results.
• Findings were similar after excluding veterans with TBI in the previous 10 years and when amyloid-PET positivity was defined using a quantitative threshold rather than consensus visual read.

The investigators noted that TBI history may act as a modifier of AD blood biomarker accuracy. As blood biomarkers are increasingly used to support AD diagnosis and determine eligibility for amyloid-targeting therapies, the authors wrote that the p-tau217/Aβ42 ratio may miss more than half of amyloid-PET–positive cases among people with prior TBI.

The study also found that amyloid-PET positivity was more common with increasing TBI exposure. Amyloid-PET positivity by visual read occurred in 18% of veterans without TBI, 27% of those with TBI and brief loss of consciousness, and 47% of those with TBI and loss of consciousness for more than 5 minutes.

Limitations included the study’s cross-sectional design, reliance on self-reported lifetime TBI history, and a cohort composed almost entirely of male Vietnam War veterans. The authors stated that findings should be validated in larger and more diverse cohorts, including women, civilians, and veterans with a broader range of TBI exposure.

Source

Rosen-Lang Y, Vrillon A, Pasternak S, et al. Prior Traumatic Brain Injury and Alzheimer Disease Blood Biomarkers. JAMA Neurol. Published online June 29, 2026. doi:10.1001/jamaneurol.2026.2042