{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:24:50Z","timestamp":1789539890526,"version":"build-2803163510"},"posted":{"date-parts":[[2025,4,7]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Bipolar disorder (BD) has been associated with an elevated risk of Alzheimer\u2019s Disease (AD). We assessed AD biomarkers in BD and tested whether epigenetic aging (EA) acceleration is a potential mechanism driving variability in these markers.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design, Setting, Participants<\/jats:title>\n                  <jats:p>Cross-sectional study of n=59 living individuals with BD and n=20 age- and sex-equated control participants, as well as analyses of postmortem brain samples (Brodmann area 9\/46) from n=46 individuals with BD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Measurements<\/jats:title>\n                  <jats:p>\n                    Amyloid beta (A\u03b2)\n                    <jats:sub>40<\/jats:sub>\n                    , A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    , and total Tau levels were measured in plasma from individuals with BD and controls, and A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    levels were measured in brains. EA and its acceleration (blood: GrimAge and DunedinPACE; brains: DNAmClock\n                    <jats:sub>Cortical<\/jats:sub>\n                    ) were estimated for all samples. Individuals with BD were split into quartiles with accelerated or slower EA if they were in the first or fourth quartiles for GrimAge acceleration (AgeAccelGrim), DunedinPACE, or DNAmClock\n                    <jats:sub>Cortical<\/jats:sub>\n                    acceleration (DNAmClock\n                    <jats:sub>Cortical<\/jats:sub>\n                    Accel).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Individuals with BD showed an increase in A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    (p=.049) and a decrease in the A\u03b2\n                    <jats:sub>42\/40<\/jats:sub>\n                    ratio (p=.035) compared to controls. A decrease in the A\u03b2\n                    <jats:sub>42\/40<\/jats:sub>\n                    ratio was also found in individuals with BD with high versus low AgeAccelGrim (p=.028). Brain A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    levels significantly correlated with DNAmClock\n                    <jats:sub>Cortical<\/jats:sub>\n                    Accel (r\n                    <jats:sup>2<\/jats:sup>\n                    =.270, p=.007), with those with high EA acceleration showing higher brain A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    after controlling for confounders (p=.008).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results provide preliminary evidence that EA may explain the variability in AD risk in individuals with BD and could act as a target for preventing dementia and AD in BD.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.06.25325186","type":"posted-content","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T01:02:14Z","timestamp":1744074134000},"source":"Crossref","is-referenced-by-count":1,"title":["Association between epigenetic aging acceleration and amyloid biomarkers in bipolar disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-2612","authenticated-orcid":false,"given":"Gabriel R.","family":"Fries","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"De La Garza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning O.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres W.","family":"Bass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila N. 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