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In contrast, associations with tau burden and cognition are less well characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We performed a cross\u2010sectional analysis of CU participants from the Anti\u2010Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4), Alzheimer's Disease Neuroimaging Initiative (ADNI), Wisconsin Registry for Alzheimer's Prevention (WRAP), and National Alzheimer's Coordinating Center (NACC) within the harmonized multi\u2010cohort Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP\u2010PHC) data. A total of 4380 CU participants were included with APOE genotype, amyloid PET, and cognitive data (memory, language, executive, and visuospatial function), including a subset of 758 with tau PET imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Compared with \u03b533, \u03b524 (\u03b2 = 18.340), \u03b534 (\u03b2 = 23.850), and \u03b544 (\u03b2 = 44.820) showed higher amyloid burden (all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; .001). Similarly, \u03b524 (OR = 4.180), \u03b534 (OR = 4.540), and \u03b544 (OR = 14.150) had higher odds of amyloid positivity (all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; .001). After adjustment for amyloid burden, \u03b54 carriers had higher tau burden in the entorhinal cortex (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.026; false discovery rate [FDR] \u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.041) and amygdala (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.040; FDR\u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003). Higher tau burden was associated with lower memory (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a0\u22120.439; FDR\u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.012) and language performance (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a0\u22120.610; FDR\u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.020).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>APOE \u03b54 showed a strong dose\u2010dependent association with amyloid, with the highest levels observed among \u03b54 homozygotes. Associations between APOE and global tau were more modest and appeared to be driven mainly by \u03b54 homozygotes, while regional analyses showed localized APOE \u03b54\u2010related associations in medial temporal regions. Independently, higher tau was associated with lower memory and language performance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dad2.70496","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:50:10Z","timestamp":1790563810000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["APOE and amyloid\u2010tau pathology in cognitively unimpaired older adults"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-7329","authenticated-orcid":false,"given":"Carlos","family":"Albarr\u00e1n Morillo","sequence":"first","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukai","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Ghanbarian","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Khorsand","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal M.","family":"Glover","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"},{"name":"Alzheimer's Disease Research Center Institute for Memory Impairments and Neurological Disorders (UCI MIND) University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Grill","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease Research Center Institute for Memory Impairments and Neurological Disorders (UCI MIND) University of California  Irvine California USA"},{"name":"Department of Psychiatry and Human Behavior University of California  Irvine California USA"},{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Ahmad","family":"Sajjadi","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders University of California  Irvine California USA"},{"name":"Alzheimer's Disease Research Center Institute for Memory Impairments and Neurological Disorders (UCI MIND) University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-4589","authenticated-orcid":false,"given":"Ali","family":"Ezzati","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders University of California  Irvine California USA"},{"name":"Alzheimer's Disease Research Center Institute for Memory Impairments and Neurological Disorders (UCI MIND) University of California  Irvine California USA"},{"name":"Department of Epidemiology and Biostatistics University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2017.03.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.10.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.263"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094806"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.05.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.11.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2018.01.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.13909"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010020\u201005099\u2010w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.08.195"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010022\u201000590\u20104"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010025\u201002000\u20106"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12173"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.065290"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1037\/neu0000835"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12668"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010022\u201005784\u2010y"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf016"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.120.257824"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000213775"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.1858"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.71031"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.71226"}],"container-title":["Alzheimer's &amp; 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