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Forty-five individuals (19 mutation carriers [EYO\u2009=\u2009\u22127.9\u2009\u00b1\u200911.7 years,\n                    <jats:italic>APP<\/jats:italic>\n                    N\u2009=\u200911;\n                    <jats:italic>PSEN1<\/jats:italic>\n                    N\u2009=\u20098]) from Swedish ADAD families participated. All received baseline 18F-Flurodeoxyglucose (FDG) PET and cognitive testing, and a subset (N\u2009=\u200926) plasma glial fibrillary acidic protein (GFAP) measurement. Follow-up data collection (including 106 FDG scans) was performed over 7.4\u2009\u00b1\u20096.4 years (visits ranged from 1\u20135, EYO\u2009=\u2009\u221225.8 to +10.3 years in mutation carriers). Mixed effects models were applied to determine longitudinal associations.\n                    <jats:italic>APP<\/jats:italic>\n                    and\n                    <jats:italic>PSEN1<\/jats:italic>\n                    mutation carriers showed different FDG uptake profiles from EYO\u2009=\u2009\u221220 to \u221210 years, with a hypermetabolism before hypometabolism in\n                    <jats:italic>PSEN1<\/jats:italic>\n                    mutation carriers. Early increases in plasma GFAP were primarily related to subcortical FDG decreases and cognitive changes in\n                    <jats:italic>APP<\/jats:italic>\n                    mutation carriers compared to non-carriers. We provide evidence for gene-dependent biomarker trajectories in ADAD.\n                  <\/jats:p>","DOI":"10.1038\/s41398-026-03829-6","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:37:06Z","timestamp":1769506626000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early functional changes and plasma GFAP in Swedish families with Autosomal Dominant Alzheimer\u2019s disease mutations"],"prefix":"10.1038","volume":"16","author":[{"given":"Emma S.","family":"Luckett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Zapater-Fajari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ove","family":"Almkvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Chiotis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5206-8651","authenticated-orcid":false,"given":"Marco","family":"Bucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Wall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-8141","authenticated-orcid":false,"given":"Elena","family":"Rodriguez-Vieitez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9949-2951","authenticated-orcid":false,"given":"Caroline","family":"Graff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-5151","authenticated-orcid":false,"given":"Agneta","family":"Nordberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"3829_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","volume":"9","author":"CR Jack","year":"2010","unstructured":"Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. 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AN has served as consultant for AG Lundbeck AB, Hoffmann La Roche, AVVA Pharmaceuticals, given lectures for Hoffman La Roche and Astra Zeneca and served on the advisory board for Dementia Platform UK. KB has served as a consultant and at advisory boards for Abbvie, AC Immune, ALZPath, AriBio, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. HZ has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All participants provided written informed consent in accordance with the Declaration of Helsinki. Ethics approval was obtained from the regional Human Ethics Committee of Stockholm and the Faculty of Medicine and Radiation Hazard Ethics Committee of Uppsala University Hospital, Sweden.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"67"}}