{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:35:26Z","timestamp":1788402926182,"version":"build-2803163510"},"reference-count":46,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:p>Background: The Apolipoprotein E (APOE) \u025b4 allele has been linked to increased tau phosphorylation and tangle formation. APOE \u025b4 carriers with elevated tau might be at the higher risk for Alzheimer\u2019s disease (AD) progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE \u025b4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether the influence of elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE \u025b4 carriers. Objective: We related \u025b4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity. Methods: Plasma p-tau181 was analyzed in 142 clinically defined AD cases and 126 matched controls. The longitudinal analysis involved 87 non-demented individuals (from population-based study) with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding. Results: Increased p-tau181 was observed for both \u025b4 carriers and non-carriers close to AD onset, but exclusively for \u025b4 carriers in the early preclinical groups (7- and 13-years pre-AD). In \u025b4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity. Conclusion: Our findings support an association of APOE \u025b4 and p-tau181 with preclinical AD and hippocampus functioning.<\/jats:p>","DOI":"10.3233\/jad-210673","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T12:09:12Z","timestamp":1639742952000},"page":"1309-1320","source":"Crossref","is-referenced-by-count":35,"title":["Association of APOE \u025b4 and Plasma p-tau181 with Preclinical Alzheimer\u2019s Disease and Longitudinal Change in Hippocampus Function"],"prefix":"10.1177","volume":"85","author":[{"given":"Alireza","family":"Salami","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Wallenberg Center for Molecular Medicine (WCMM), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Aging Research Center, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Adolfsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micael","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Integrative Medical Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Lundquist","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Statistics, USBE Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelie Nordin","family":"Adolfsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK"},{"name":"UK Dementia Research Institute at UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Nyberg","sequence":"additional","affiliation":[{"name":"Department of Integrative Medical Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Wallenberg Center for Molecular Medicine (WCMM), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of 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