{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:49:46Z","timestamp":1768571386792,"version":"3.49.0"},"posted":{"date-parts":[[2025,8,19]]},"group-title":"Neurology","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>\n                    Plasma biomarkers of Alzheimer\u2019s disease (AD) pathology are frequently tested in specialized research settings, limiting generalizability of findings. Using electronic health records and banked plasma, we evaluated plasma biomarkers \u2013 phosphorylated tau 217 (p-tau\n                    <jats:sub>217<\/jats:sub>\n                    ), \u03b2-amyloid 1-42\/1-40 (A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    ) and p-tau\n                    <jats:sub>217<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \u2013 in a real-world, diverse clinical population with multimorbidities.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Participants (n=617; 44% Black\/African American; 41% female) were selected from the University of Pennsylvania Medicine BioBank with plasma assayed using Fujirebio Lumipulse. International Classification of Diseases (ICD) Ninth and Tenth Revision codes determined AD dementia (ADD; n=43), mild-cognitive impairment (MCI; n=140), unspecified\/non-AD cognitive impairment (CI; n=106), and cognitively normal cases (n=328), and other medical histories. APOE \u03b54, body mass index (BMI), metrics of kidney function (\n                    <jats:italic>e.g.<\/jats:italic>\n                    , eGFR), and liver disease were derived from electronic health records. Multivariable models identified factors related to plasma levels. Previously established cutpoints classified AD status (\u201cAD+\u201d, \u201cAD-\u201d, or \u201cIntermediate\u201d).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Plasma p-tau\n                    <jats:sub>217<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    had the strongest association with known AD-related factors \u2013 MCI, ADD, future progression to MCI\/ADD, age, and APOE \u03b54 \u2013 compared to p-tau\n                    <jats:sub>217<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    . Plasma p-tau\n                    <jats:sub>217<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    was also associated with eGFR, diabetes, and history of hearing loss. Importantly, AD-related factors were most frequent\/severe for AD+ classification by p-tau\n                    <jats:sub>217<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    , while medical morbidities were most frequent\/severe for Intermediate classification. Exploratory analyses test p-tau\n                    <jats:sub>217<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    adjusted for eGFR to eliminate its influence on plamsa levels.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>\n                    In this real-world dataset, we identified effects of multimorbidities on plasma biomarkers, especially kidney function. The p-tau\n                    <jats:sub>217<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    ratio had low rates of Intermediate classification and may help to account for multimorbidity effects on plasma levels.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.16.25333799","type":"posted-content","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T14:17:50Z","timestamp":1755613070000},"source":"Crossref","is-referenced-by-count":0,"title":["Electronic health records to test multimorbidity influences to plasma biomarker interpretation for Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-2766","authenticated-orcid":false,"given":"Katheryn A.Q.","family":"Cousins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-6892","authenticated-orcid":false,"given":"Rory","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen","family":"Morse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anurag","family":"Verma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-3976","authenticated-orcid":false,"given":"Christopher A.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyra S.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Serper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Dehghani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penn Medicine","family":"BioBank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7581-6405","authenticated-orcid":false,"given":"Corey T.","family":"McMillan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward B.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Wolk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025082110551329000_2025.08.16.25333799v1.1","doi-asserted-by":"crossref","unstructured":"Cousins KAQ , Phillips JS , Das SR , et al. 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