{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T21:39:48Z","timestamp":1777066788435,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,21]]},"group-title":"Neuroscience","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"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":[[2026,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Alzheimer\u2019s disease (AD) neuropathological changes can be detected with blood-based biomarkers during the long preclinical phase that precedes clinical diagnosis. Tau phosphorylated at threonine 217 (p-tau217) has been found to closely correlate with brain A\u03b2 burden. A recent large-scale cross-sectional study showed elevated p-tau217 concentrations in older individuals (Aarsland et al., 2025). This increase was higher in those with AD dementia and mild cognitive impairment (MCI), and lower in those with intact cognition and higher educational attainment. Thus, intact cognition and higher education may be associated with lower levels of AD neuropathological changes. Here we tested this hypothesis using longitudinal data from the population-based\n                  <jats:italic>Betula<\/jats:italic>\n                  study (n=1005; 1531 samples). The results revealed increases with increasing age over 10 years in p-tau217, where individuals with accelerated episodic-memory decline had the strongest increase. There were no differences in p-tau217 trajectories between individuals with lower or higher education or with well-maintained or age-typical decline in episodic memory. The lack of association with education was further replicated in the independent BioFINDER-2 cohort. These findings underscore the value of plasma p-tau217 for detecting early pathological changes in population-based settings but provide no support that individuals with well-maintained episodic memory or high educational attainment are spared from neuropathological changes.\n                <\/jats:p>","DOI":"10.64898\/2026.04.16.718397","type":"posted-content","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:55:17Z","timestamp":1776783317000},"source":"Crossref","is-referenced-by-count":0,"title":["Stable episodic memory and high education do not influence the rate of Alzheimer\u2019s disease pathology as measured by plasma p-tau217"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-8504","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Avelar-Pereira","sequence":"first","affiliation":[{"name":"Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden"},{"name":"Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-8788","authenticated-orcid":false,"given":"Nicola","family":"Spotorno","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8287-0754","authenticated-orcid":false,"given":"Anna","family":"Ordu\u00f1a Dolado","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3178-1586","authenticated-orcid":false,"given":"Divya","family":"Bali","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelie Nordin","family":"Adolfsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Psychiatry, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8885-7724","authenticated-orcid":false,"given":"Niklas","family":"Mattsson-Carlgren","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"},{"name":"Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-1930","authenticated-orcid":false,"given":"Sebastian","family":"Palmqvist","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-8378","authenticated-orcid":false,"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-7286","authenticated-orcid":false,"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3367-1746","authenticated-orcid":false,"given":"Lars","family":"Nyberg","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Functional Brain Imaging, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Medical and Translational Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Diagnostics and Intervention, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026042414001029000_2026.04.16.718397v1.1","unstructured":"Aarsland, D. , Sunde, A. L. , Tovar-Rios, D. A. , Leuzy, A. , Fladby, T. , Zetterberg, H. , \u2026 & Ashton, N. J. (2025). Prevalence of Alzheimer\u2019s disease pathology in the community. Nature, 1\u20135."},{"issue":"3","key":"2026042414001029000_2026.04.16.718397v1.2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","article-title":"Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology","volume":"81","year":"2024","journal-title":"JAMA neurology"},{"key":"2026042414001029000_2026.04.16.718397v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02074-w"},{"issue":"1","key":"2026042414001029000_2026.04.16.718397v1.4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13195-024-01391-1","article-title":"Effects of certain pre-analytical factors on the performance of plasma phospho-tau217","volume":"16","year":"2024","journal-title":"Alzheimer\u2019s Research & Therapy"},{"key":"2026042414001029000_2026.04.16.718397v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.02.009."},{"issue":"8","key":"2026042414001029000_2026.04.16.718397v1.6","doi-asserted-by":"crossref","first-page":"5617","DOI":"10.1002\/alz.14073","article-title":"Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer\u2019s disease","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"9","key":"2026042414001029000_2026.04.16.718397v1.7","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1038\/s41591-025-03912-3","article-title":"Education does not affect memory decline or brain aging","volume":"31","year":"2025","journal-title":"NATURE MEDICINE"},{"issue":"8","key":"2026042414001029000_2026.04.16.718397v1.8","doi-asserted-by":"crossref","first-page":"e374","DOI":"10.1016\/S2666-7568(23)00079-X","article-title":"Brain structure and phenotypic profile of superagers compared with age-matched older adults: a longitudinal analysis from the Vallecas Project","volume":"4","year":"2023","journal-title":"The Lancet Healthy Longevity"},{"key":"2026042414001029000_2026.04.16.718397v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03605-x"},{"issue":"5","key":"2026042414001029000_2026.04.16.718397v1.10","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s43587-023-00403-3","article-title":"Blood biomarkers for Alzheimer\u2019s disease in clinical practice and trials","volume":"3","year":"2023","journal-title":"Nature aging"},{"key":"2026042414001029000_2026.04.16.718397v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"issue":"8","key":"2026042414001029000_2026.04.16.718397v1.12","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026042414001029000_2026.04.16.718397v1.13","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.12000"},{"issue":"7","key":"2026042414001029000_2026.04.16.718397v1.14","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1017\/S1041610219001844","article-title":"Memory profiles predict dementia over 23\u201328 years in normal but not successful aging","volume":"35","year":"2023","journal-title":"International Psychogeriatrics"},{"key":"2026042414001029000_2026.04.16.718397v1.15","doi-asserted-by":"publisher","DOI":"10.1177\/1529100620920576"},{"issue":"4","key":"2026042414001029000_2026.04.16.718397v1.16","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1001\/jamaneurol.2022.5272","article-title":"Prediction of longitudinal cognitive decline in preclinical Alzheimer disease using plasma biomarkers","volume":"80","year":"2023","journal-title":"JAMA neurology"},{"key":"2026042414001029000_2026.04.16.718397v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/S41591-022-01822-2"},{"key":"2026042414001029000_2026.04.16.718397v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01925-w"},{"key":"2026042414001029000_2026.04.16.718397v1.19","doi-asserted-by":"publisher","DOI":"10.1080\/13825580490511026"},{"key":"2026042414001029000_2026.04.16.718397v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101184"},{"key":"2026042414001029000_2026.04.16.718397v1.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101644118"},{"key":"2026042414001029000_2026.04.16.718397v1.22","doi-asserted-by":"publisher","DOI":"10.1001\/JAMA.2020.12134"},{"key":"2026042414001029000_2026.04.16.718397v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02450-0"},{"key":"2026042414001029000_2026.04.16.718397v1.24","doi-asserted-by":"crossref","unstructured":"Petersen, K. K. , Mil\u00e0-Alom\u00e0, M. , Li, Y. , Du, L. , Xiong, C. , Tosun, D. , \u2026 & Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium Plasma A\u03b2 and Phosphorylated Tau as Predictors of Amyloid and Tau Positivity in Alzheimer\u2019s Disease Project Team. (2026). Predicting onset of symptomatic Alzheimer\u2019s disease with plasma p-tau217 clocks. Nature Medicine, 1\u201310.","DOI":"10.1038\/s41591-026-04206-y"},{"issue":"3","key":"2026042414001029000_2026.04.16.718397v1.25","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/1531-8249(199903)45:3<358::AID-ANA12>3.0.CO;2-X","article-title":"Tangles and plaques in nondemented aging and \u201cpreclinical\u201d Alzheimer\u2019s disease","volume":"45","year":"1999","journal-title":"Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society"},{"key":"2026042414001029000_2026.04.16.718397v1.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2900-12.2013"},{"key":"2026042414001029000_2026.04.16.718397v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.101005"},{"key":"2026042414001029000_2026.04.16.718397v1.28","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617702813248"},{"issue":"9","key":"2026042414001029000_2026.04.16.718397v1.29","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.jalz.2018.07.219","article-title":"Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance","volume":"16","author":"Reserve, Resilience and Protective Factors PIA Empirical Definitions and Conceptual Frameworks Workgroup","year":"2020","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"2","key":"2026042414001029000_2026.04.16.718397v1.30","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/brain\/awae346","article-title":"A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests","volume":"148","year":"2025","journal-title":"Brain"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.16.718397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T21:00:22Z","timestamp":1777064422000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.16.718397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":30,"URL":"https:\/\/doi.org\/10.64898\/2026.04.16.718397","relation":{},"subject":[],"published":{"date-parts":[[2026,4,21]]},"subtype":"preprint"}}