{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:00:38Z","timestamp":1790773238755,"version":"4.1.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG066507"],"award-info":[{"award-number":["P30 AG066507"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["A2023004S"],"award-info":[{"award-number":["A2023004S"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Johns Hopkins Armstrong Family Human Aging Project\/Center for Innovative Medicine Scholar Award"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tau pathology begins to accumulate in the medial temporal lobe in many individuals in middle age. Some individuals develop amyloid pathology, more advanced tau pathology (Braak stage), and higher levels of CA1 hippocampal tau pathology in the context of Alzheimer's disease. Others never develop significant amyloid pathology; in these cases, hippocampal tau pathology can be CA2-predominant and tends not to accumulate past intermediate stages. But factors associated with the early formation of these tau patterns is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The objective of this study is to examine demographic, genetic (\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      ), and pathologic factors associated with the emergence of hippocampal tau pathology patterns in middle age.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We identified 89 individuals with hippocampal tau pathology ages 65 and younger. These cases were assessed for tau stage, amyloid plaques, and\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      status. Hippocampal tau pathology in CA1 and CA2 was scored semi-quantitatively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a younger aging population, tau pathology initially deposits at low levels in CA1 and CA2. In the presence of amyloid, tau pathology is increased in both CA1 and CA2, but with a shift toward a greater proportion of cases with higher tau pathology in CA1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patterns of tau pathology in middle age are strongly associated with amyloid plaques, including increased CA1 and CA2 pathology and a greater proportion of CA1-predominant cases. In the absence of amyloid, tau pathology shows a normal (Gaussian) distribution between CA1 and CA2. These tau pathology distributions at younger ages are similar to the patterns seen at older ages in AD and PART.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261443643","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:20:39Z","timestamp":1776954039000},"page":"1527-1535","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Amyloid plaques associated with shift in patterns of hippocampal tau pathology in middle age"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7274-0791","authenticated-orcid":false,"given":"Rocio Fernanda","family":"Rodriguez-Reyes","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9678-1777","authenticated-orcid":false,"given":"Haidan","family":"Guo","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2611-3614","authenticated-orcid":false,"given":"Maria","family":"Luongo","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5042-3366","authenticated-orcid":false,"given":"Laura","family":"Gomez-Isaza","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Pletnikova","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine"},{"name":"University at Buffalo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-6673","authenticated-orcid":false,"given":"Juan C.","family":"Troncoso","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine"},{"name":"Johns Hopkins University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5340-148X","authenticated-orcid":false,"given":"Meaghan","family":"Morris","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine"},{"name":"Kavli Neuroscience Discovery Institute, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1349-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03911-7"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115422"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199708000-00011"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlad064"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.07.215"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01233-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90590-H"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31825018f7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70613"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-025-02921-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-025-02920-4"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlaa153"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlab032"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1894-z"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.07.007"},{"key":"e_1_3_3_19_2","volume-title":"Atlas of the human brain","author":"Mai JK","year":"2015","unstructured":"Mai JK, Majtanik M, Paxinos G. 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