{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T21:31:11Z","timestamp":1768858271684,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,15]]},"group-title":"Neurology","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>Traumatic brain injury (TBI) is a risk factor for dementia and is known to impact levels of several Alzheimer\u2019s disease (AD) blood biomarkers. Plasma pTau217\/ A\u03b242 ratio has been reported to be 90% accurate for detection of brain amyloid in civilian cohorts.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To evaluate the accuracy of emerging AD blood biomarkers in Veterans with and without TBI history.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>We assessed the performance of the FDA-approved plasma pTau217\/A\u03b242 ratio and plasma levels of pTau217 and A\u03b242\/40 ratio for detecting brain amyloid-\u03b2 positivity (e.g., amyloid-PET consensus visual read). We compared biomarkers\u2019 accuracy in Veterans with no TBI (N=93), TBI with loss of consciousness (LOC) 0-5 minutes (N=89), and TBI with LOC &gt;5 minutes (N=90).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Cross-sectional cohort study using existing data and banked plasma from the Alzheimer\u2019s Disease Neuroimaging Initiative Department of Defense (ADNI-DOD) study.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>272 older Vietnam Veterans without dementia (83% cognitively unimpaired, 17% mild cognitive impairment), median (IQR) age 69 (67,72) years, 270\/272 male, who had amyloid-PET and concurrently collected banked plasma available for analysis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Amyloid-PET positivity prevalence was 30.5%. Plasma pTau217\/A\u03b242 ratio was highly accurate (90%) in Veterans with no TBI, but not in Veterans with TBI with LOC 0-5 minutes (78% accuracy,\n                    <jats:italic>P<\/jats:italic>\n                    =0.027 vs no TBI) nor in Veterans with TBI with LOC&gt;5 minutes (63% accuracy,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001 vs no TBI). Results were similar for plasma pTau217 alone and plasma A\u03b242\/40 ratio. Results were also similar after excluding Veterans with TBI within the past 10 years, or when amyloid-PET positivity was defined using a quantitative threshold rather than consensus visual read.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Prior TBI is a modifier of AD biomarkers accuracy in prediction of brain amyloid-PET positivity. Caution is advised in interpreting AD blood test results in this context. Further research is warranted to refine precision AD diagnosis in Veterans and civilians with TBI history.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Question<\/jats:title>\n                  <jats:p>What is the accuracy of the plasma pTau217\/A\u03b242 ratio test for detecting amyloid-PET positivity for Alzheimer\u2019s disease (AD) diagnosis in older Veterans with and without a history of traumatic brain injury (TBI)?<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>In this cross-sectional study (n=272), plasma pTau217\/A\u03b242 ratio test accuracy was 90% in Veterans without TBI history, but was significantly lower (63-78% accuracy) in Veterans with TBI history, with lowest accuracy in those with greater TBI severity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Meaning<\/jats:title>\n                  <jats:p>TBI history and severity is a modifier of AD blood test accuracy in prediction of brain amyloid-PET positivity.AD blood tests should be interpreted with caution in Veterans and civilians with TBI history.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.13.26344009","type":"posted-content","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T17:00:28Z","timestamp":1768496428000},"source":"Crossref","is-referenced-by-count":0,"title":["Effect of prior traumatic brain injury on Alzheimer\u2019s disease blood biomarkers in Vietnam Veterans"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8642-4276","authenticated-orcid":false,"given":"Yael Rosen","family":"Lang","sequence":"first","affiliation":[{"name":"Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat-Gan, 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