{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:03:54Z","timestamp":1760403834660,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":57,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["SG\u2010 21\u2010818099\u2010EPAD"],"award-info":[{"award-number":["SG\u2010 21\u2010818099\u2010EPAD"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp; Dem Diag Ass &amp; Dis Mo"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Whether temporal proximity to parental onset of dementia (PPO) can be used to estimate timing of the preclinical stage of sporadic Alzheimer's disease (AD) remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We investigated cross\u2010sectionally adults aged\u00a0&gt;\u00a050 without dementia included in the European Prevention of Alzheimer's Dementia (EPAD) study. PPO was tested as a predictor of quantitative levels of cerebrospinal fluid (CSF) \u03b2\u2010amyloid (1\u201042) (A\u03b21\u201042) in those with a parental history of dementia (<jats:italic>n<\/jats:italic>\u00a0=\u00a0688) and of phosphorylated tau (p\u2010tau) and EPAD neuropsychological examination (ENE) subscores in an amyloid positive subgroup (<jats:italic>n<\/jats:italic>\u00a0=\u00a0226). Possible interactions were explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Shorter PPO predicted lower CSF A\u03b21\u201042 level (\u03b2\u00a0=\u00a09.357; T\u00a0=\u00a04.161; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001), interacting\u00a0with apolipoprotein E (APOE) \u2010\ud835\udf004 carriage in a\u00a0dose\u2010dependent manner. Concomitant APOE\u2010\ud835\udf002 carriage appeared to provide protection. PPO did not predict p\u2010tau levels or cognitive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>PPO may provide a valid method of stratifying risk of early AD pathologic change in APOE\u2010\ud835\udf004 carriers, with empirical and clinical applications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Proximity to age of parental dementia onset can predict amyloid accrual<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effect is APOE\u2010\ud835\udf004 dose\u2010dependent and APOE\u2010\ud835\udf002 appears to provide protection<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>PPO does not appear to predict further advancement along the AD continuum<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the era of anti\u2010amyloid treatments, this may inform timing of amyloid screening<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Used as an empirical metric, PPO could help elucidate the natural history of LOAD<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70092","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:43:43Z","timestamp":1741736623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accrual of Alzheimer's disease pathology as a function of proximity to parental dementia onset"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-8546","authenticated-orcid":false,"given":"Elina T.","family":"Ziukelis","sequence":"first","affiliation":[{"name":"Institute of Psychiatry, Psychology &amp; Neuroscience at King's College London  London UK"},{"name":"South London &amp; Maudsley NHS Foundation Trust  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elijah","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine University of Cambridge, Level E4 Cambridge Biomedical Campus  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Scottish Brain Sciences, Gyleview House  Edinburgh UK"},{"name":"Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences University of Edinburgh  Edinburgh UK"},{"name":"School of Medicine University of St Andrews  St Andrews UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine University of Cambridge, Level E4 Cambridge Biomedical Campus  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology &amp; Neuroscience at King's College London  London UK"},{"name":"South London &amp; Maudsley NHS Foundation Trust  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the European Prevention of Alzheimer's Disease (EPAD) Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.15m09989"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000596"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"issue":"8","key":"e_1_2_7_6_1","first-page":"P85","article-title":"Age\u2010associated trajectories of biomarkers in early\u2010onset Alzheimer's disease, for the Alzheimer's Prevention Initiative","volume":"4","author":"Chen K","year":"2012","journal-title":"Alzheimer Dement"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105714"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.12.008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42596-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.221"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.135"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.1491"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy093"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.117749"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.02.008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010527"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.5135"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30367-6"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002923"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-021017"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12292"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.06.2365"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.07.154"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.1.139"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.60.2.190"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30412-9"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-021-00583-9"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1037\/neu0000561"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160766"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180507"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00533-w"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30193-4"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02249-0"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.10.001"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww015"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu367"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4017"}],"container-title":["Alzheimer's &amp; 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