{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:54:54Z","timestamp":1791222894489,"version":"4.1.0"},"posted":{"date-parts":[[2026,10,5]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Mental Health","award":["R01 MH108509"],"award-info":[{"award-number":["R01 MH108509"]}]},{"name":"National Institute of Mental Health","award":["T32 MH019986"],"award-info":[{"award-number":["T32 MH019986"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,5]]},"abstract":"<jats:p>Objectives: To determine whether distinct anxiety phenotypes (rumination, global anxiety and worry; RAW) are associated with plasma brain-derived (BD) phosphorylated-tau (p-tau) biomarkers of Alzheimer's disease (AD) in older adults.\nDesign: Cross-sectional observational study.\nMethods: Participants were 89 older adults aged 50\u2265years (mean age 64.3\u00b18.8 years) enrolled in the RAW Brain study (R01 MH108509) in Pittsburgh, Pennsylvania. Anxiety phenotypes were assessed using the Penn State Worry Questionnaire (PWSQ\u226550), Rumination Subscale from the Response Style Questionnaire (RSQ&gt;50), and Hamilton Anxiety Rating Scale (HARS&gt;17). Participants were classified as High-RAW if they exceeded established severity thresholds on \u22651 domain; continuous anxiety scores were used for primary analyses. Plasma BD-tau, BD-p-tau181, BD-p-tau217, and BD-p-tau231, and matched non-BD versions were quantified using the NULISAseq\u2122 CNS Panel. Associations between anxiety phenotypes and tau biomarkers were examined using multivariable linear regression adjusted for age, sex, and APOE4 status, with Benjamini-Hochberg false discovery rate correction.\nResults: Greater global anxiety was associated with higher plasma BD-p-tau181 (\u03b2=0.308, 95% CI [0.003,0.048], p=0.047). This association was also observed categorically (adjusted Cohen's d=0.462, p=0.049). Worry and rumination were not associated with BD-p-tau181, and no anxiety phenotypes were associated with BD-tau, BD-p-tau217, BD-p-tau231, or corresponding non-BD alternatives. \nConclusions: Greater late-life global anxiety, but not worry or rumination, was selectively associated with higher plasma BD-p-tau181. These findings extend epidemiologic evidence linking anxiety to AD risk by identifying a biologically specific blood-based correlate linking anxiety with AD-related p-tau biology. Longitudinal studies incorporating amyloid and tau biomarker confirmation are needed to determine whether anxiety precedes, accompanies, or results from early AD pathophysiology.<\/jats:p>","DOI":"10.64898\/2026.10.02.26364610","type":"posted-content","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:20:31Z","timestamp":1791220831000},"source":"Crossref","is-referenced-by-count":0,"title":["Association between plasma brain-derived p-tau variants and anxiety phenotypes in older adults"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0489-4315","authenticated-orcid":false,"given":"Ana Paula","family":"Costa","sequence":"first","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmet T","family":"Karim","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa F","family":"Farinas","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nya","family":"Nicholson","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M","family":"Geissinger","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zeng","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana L","family":"Tudorascu","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryl A","family":"Butters","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-4358","authenticated-orcid":false,"given":"Thomas K","family":"Karikari","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Andreescu","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.10.02.26364610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:20:31Z","timestamp":1791220831000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.10.02.26364610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.10.02.26364610","relation":{},"subject":[],"published":{"date-parts":[[2026,10,5]]},"subtype":"preprint"}}