{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:20:34Z","timestamp":1793578834980,"version":"4.5.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Alz Res Therapy"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Alzheimer\u2019s disease (AD) is characterized by the accumulation of amyloid-\u03b2 (A\u03b2) plaques, neurofibrillary tau tangles, and neurodegeneration in the brain parenchyma. Here, we aimed to (i) assess differences in blood and imaging biomarkers used to evaluate neurodegeneration among cognitively unimpaired <jats:italic>APOE<\/jats:italic> \u03b54 homozygotes, heterozygotes, and non-carriers with varying risk for sporadic AD, and (ii) to determine how different cerebral pathologies (i.e., A\u03b2 deposition, medial temporal atrophy, and cerebrovascular pathology) contribute to blood biomarker concentrations in this sample.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Sixty <jats:italic>APOE<\/jats:italic> \u03b54 homozygotes (<jats:italic>n<\/jats:italic>\u2009=\u200919), heterozygotes (<jats:italic>n<\/jats:italic>\u2009=\u200921), and non-carriers (<jats:italic>n<\/jats:italic>\u2009=\u200920) ranging from 60 to 75 years, were recruited in collaboration with Auria biobank (Turku, Finland). Participants underwent A\u03b2-PET ([<jats:sup>11<\/jats:sup>C]PiB), structural brain MRI including T1-weighted and T2-FLAIR sequences, and blood sampling for measuring serum neurofilament light chain (NfL), plasma total tau (t-tau), plasma N-terminal tau fragments (NTA-tau) and plasma glial fibrillary acidic protein (GFAP). [<jats:sup>11<\/jats:sup>C]PiB standardized uptake value ratio was calculated for regions typical for A\u03b2 accumulation in AD. MRI images were analysed for regional volumes, atrophy scores, and volumes of white matter hyperintensities. Differences in biomarker levels and associations between blood and imaging biomarkers were tested using uni- and multivariable linear models (unadjusted and adjusted for age and sex).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Serum NfL concentration was increased in <jats:italic>APOE<\/jats:italic> \u03b54 homozygotes compared with non-carriers (mean 21.4 pg\/ml (SD 9.5) vs. 15.5 pg\/ml (3.8), <jats:italic>p<\/jats:italic>\u2009=\u20090.013), whereas other blood biomarkers did not differ between the groups (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.077 for all). From imaging biomarkers, hippocampal volume was significantly decreased in <jats:italic>APOE<\/jats:italic> \u03b54 homozygotes compared with non-carriers (6.71\u00a0ml (0.86) vs. 7.2\u00a0ml (0.7), <jats:italic>p<\/jats:italic>\u2009=\u20090.029). In the whole sample, blood biomarker levels were differently predicted by the three measured cerebral pathologies; serum NfL concentration was associated with cerebrovascular pathology and medial temporal atrophy, while plasma NTA-tau associated with medial temporal atrophy. Plasma GFAP showed significant association with both medial temporal atrophy and A\u03b2 pathology. Plasma t-tau concentration did not associate with any of the measured pathologies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Only increased serum NfL concentrations and decreased hippocampal volume was observed in cognitively unimpaired APOE\u03b54 homozygotes compared to non-carriers. In the whole population the concentrations of blood biomarkers were affected in distinct ways by different pathologies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13195-024-01477-w","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T06:01:48Z","timestamp":1716012108000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Blood biomarkers of neurodegeneration associate differently with amyloid deposition, medial temporal atrophy, and cerebrovascular changes in APOE \u03b54-enriched cognitively unimpaired elderly"],"prefix":"10.1186","volume":"16","author":[{"given":"Mikko","family":"Koivum\u00e4ki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ekblad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Lantero-Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K.","family":"Karikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semi","family":"Helin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riitta","family":"Parkkola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyrki","family":"L\u00f6tj\u00f6nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha O.","family":"Rinne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anniina","family":"Snellman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,18]]},"reference":[{"issue":"2","key":"1477_CR1","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/alz.12694","volume":"19","author":"A Gustavsson","year":"2023","unstructured":"Gustavsson A, Norton N, Fast T, Fr\u00f6lich L, Georges J, Holzapfel D, et al. 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KB has served as a consultant and at advisory boards for Acumen, ALZPath, 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.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"112"}}