{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:21:05Z","timestamp":1790889665107,"version":"4.1.0"},"reference-count":84,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K24AG045334"],"award-info":[{"award-number":["K24AG045334"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1R01AG057848\u201001A1"],"award-info":[{"award-number":["1R01AG057848\u201001A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["5R01AG038465\u201009"],"award-info":[{"award-number":["5R01AG038465\u201009"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The spatial heterogeneity of tau deposition is closely linked to clinical variants of Alzheimer's disease (AD). Detecting these patterns in the preclinical stage is challenging, but second\u2010generation tau tracers provide a unique opportunity to do so.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used independent component analysis (ICA) and tau positron emission tomography (PET) imaging with the 18F\u2010MK6240 tracer in 590 cognitively healthy adults (mean age 66.58\u00a0\u00b1\u00a05.13 years, 340 females) to identify tau patterns in the preclinical stage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Using all individuals, seven distinct patterns emerged, with medial temporal lobe (MTL) involvement associated with age, A\u03b2 burden, apolipoprotein E (APOE) genotype, and plasma total tau. Bilateral amygdala\u2010hippocampus tau deposition was associated negatively with memory (\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0=\u00a0\u22122.64,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01), while broader neocortical patterns, especially asymmetric ones, were linked to deficits in language (\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0&lt;\u00a0\u22123.13,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.002) and reasoning (\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0&lt;\u00a0\u22122.63,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings advance our understanding of preclinical tau heterogeneity, offering new insights for early AD intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Seven tau deposition patterns were identified in preclinical stages of AD, including medial temporal lobe and asymmetric neocortical patterns.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Medial temporal lobe patterns were strongly linked to age, APOE genotype, A\u03b2 burden, and plasma total tau levels.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Neocortical patterns, especially asymmetric ones, were linked to domain\u2010specific cognitive deficits, notably in language and reasoning.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This research highlights the potential of using tau deposition patterns for early detection and tailoring interventions in preclinical AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70153","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T23:50:21Z","timestamp":1747093821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Heterogeneous tau deposition patterns in the preclinical stage link to domain\u2010specific cognitive deficits"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3900-9603","authenticated-orcid":false,"given":"Seyed Hani","family":"Hojjati","sequence":"first","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria C.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Health Solutions Arizona State University  Phoenix Arizona USA"},{"name":"School of Mathematics and Statistics Arizona State University  Phoenix Arizona USA"},{"name":"Department of Neurology University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Khalafi","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bardiya Ghaderi","family":"Yazdi","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Foldi","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Neurology Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mony","family":"de Leon","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaakov","family":"Stern","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Vagelos College of Physicians and Surgeons Columbia University  New York New York USA"},{"name":"Department of Neurology Vagelos College of Physicians and Surgeons Columbia University  New York New York USA"},{"name":"Gertrude H. Sergievsky Center Vagelos College of Physicians and Surgeons Columbia University  New York New York USA"},{"name":"Department of Psychiatry Vagelos College of Physicians and Surgeons Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Luchsinger","sequence":"additional","affiliation":[{"name":"Department of Medicine Columbia University Irving Medical Center  New York New York USA"},{"name":"Department of Epidemiology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qolamreza R.","family":"Razlighi","sequence":"additional","affiliation":[{"name":"Department of Radiology Brain Health Imaging Institute, Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0067-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01150-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.06.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102749"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp062"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1525-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835a30f4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau5732"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.154146"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1272946"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx243"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00021-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70156-9"},{"issue":"1","key":"e_1_2_9_16_1","first-page":"P05","article-title":"Neuroimaging correlates of pathologically\u2010defined atypical Alzheimer's disease (P05.049)","volume":"78","author":"Whitwell J","year":"2012","journal-title":"Neurology"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A7613"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170740"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23874"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01309-6"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2017.09.018"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx353"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx320"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-020-05099-w"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1356656"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2021.769982"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210419"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.063715"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2025.01.005"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103409"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-231362"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.076456"},{"key":"e_1_2_9_33_1","article-title":"Between\u2010networks hyperconnectivity is induced by beta\u2010amyloid and may facilitate tau spread","author":"Hojjati SH","year":"2024","journal-title":"Medrxiv"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"issue":"365","key":"e_1_2_9_35_1","first-page":"1","article-title":"Advanced normalization tools (ANTS)","volume":"2","author":"Avants BB","year":"2009","journal-title":"Insight J"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.003"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.02.010"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1122"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","unstructured":"SahaDK BohsaliA SahaR HajjarI CalhounVD.A Multivariate Method for Estimating and comparing whole brain functional connectomes from fMRI and PET data. InProceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society EMBS;2023.","DOI":"10.1109\/EMBC40787.2023.10340631"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.7437"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3932(92)90104-T"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.62.4.556"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5371(73)80034-9"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10280"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205018666211207094121"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.33396\/1728-0869-2020-10-55-64"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.028"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24711"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf2362"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25142"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.0676"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.07.050"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12173"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00590-4"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.4666"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.006"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118689"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.027"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1349-0"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01225-3"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0342-8"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1271"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-0277(02)00185-3"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.03.063"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5587-06.2007"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.024"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.01.018"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-01-00353.1997"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.04.062"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.101823"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011270"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02036-6"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww027"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws076"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.020"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103416"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd1327"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz026"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28896-3"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcz027"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.12917"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2007.34"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70153","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70153","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:32:14Z","timestamp":1789558334000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":84,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/alz.70153"],"URL":"https:\/\/doi.org\/10.1002\/alz.70153","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70153"}}