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Brain amyloid-\u03b2 (A\u03b2) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of A\u03b2 dynamics and depression. The aim of this study was to test if plasma A\u03b2 levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-\u03b2\n                    <jats:sub>1-40<\/jats:sub>\n                    (A\u03b240) and amyloid-\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    (A\u03b242) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the A\u03b242\/A\u03b240 plasma ratio was significantly and steadily lower in depressed subjects compared to controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). At screening, A\u03b242\/A\u03b240 plasma did not correlate with depression severity (as measured with Hamilton Depression Scale) or cognitive performance (as measured with Mini-Mental State Examination) but was associated to depression severity at 3\u2009years after adjustment for age, education, cognitive performance, and antidepressants use. This study showed that reduced plasma A\u03b242\/A\u03b240 ratio is consistently associated with LLMD diagnosis and that increased severity of depression at baseline predicted low A\u03b242\/A\u03b240 ratio at 3\u2009years. Future studies are needed to confirm these findings and examine if the consistently lower plasma A\u03b242\/A\u03b240 ratio in LLMD reflects increased brain amyloid deposition, as observed in AD subjects, and an increased risk for progressive cognitive decline and AD.\n                  <\/jats:p>","DOI":"10.1038\/s41398-022-02077-8","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T14:16:03Z","timestamp":1659017763000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Plasma Amyloid-\u03b2 dynamics in late-life major depression: a longitudinal study"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8075-4253","authenticated-orcid":false,"given":"Nunzio","family":"Pomara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-6179","authenticated-orcid":false,"given":"Chelsea Reichert","family":"Plaska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Ramos-Cejudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo S.","family":"Osorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-8556","authenticated-orcid":false,"given":"Anilkumar","family":"Pillai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno P.","family":"Imbimbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"2077_CR1","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1001\/archneur.60.5.753","volume":"60","author":"RC Green","year":"2003","unstructured":"Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D, et al. 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KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD\/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. All unrelated to the work presented in this paper. R.S.O. is a member of \u2018The Alliance for Sleep\u2019 which is sponsored by Idorsia U.S.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"301"}}