{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:27:56Z","timestamp":1789612076023,"version":"build-2803163510"},"reference-count":78,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Tau phosphorylated at threonine\u2010217 (pT217\u2010tau) is a novel fluid\u2010based biomarker that predicts onset of Alzheimer's disease (AD) symptoms, but little is known about how pT217\u2010tau arises in the brain, as soluble pT217\u2010tau is dephosphorylated\n                      <jats:italic>post mortem<\/jats:italic>\n                      in humans.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used multilabel immunofluorescence and immunoelectron microscopy to examine the subcellular localization of early\u2010stage pT217\u2010tau in entorhinal and prefrontal cortices of aged macaques with naturally occurring tau pathology and assayed pT217\u2010tau levels in plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>pT217\u2010tau was aggregated on microtubules within dendrites exhibiting early signs of degeneration, including autophagic vacuoles. It was also seen trafficking between excitatory neurons within synapses on spines, where it was exposed to the extracellular space, and thus accessible to cerebrospinal fluid (CSF)\/blood. Plasma pT217\u2010tau levels increased across the age span and thus can serve as a biomarker in macaques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These data help to explain why pT217\u2010tau predicts degeneration in AD and how it gains access to CSF and plasma to serve as a fluid biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13737","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T07:00:17Z","timestamp":1709708417000},"page":"2843-2860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Nanoscale imaging of pT217\u2010tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early\u2010stage neurodegeneration"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-3067","authenticated-orcid":false,"given":"Dibyadeep","family":"Datta","sequence":"first","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Perone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denethi","family":"Wijegunawardana","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury M.","family":"Morozov","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Arellano","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Duque","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongcong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"van Dyck","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Kate P.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F. T.","family":"Arnsten","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.12134"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0781-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.5272"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202217123"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00403-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00070-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12192"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.11.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv236"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy152"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-12679-1_1"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.09.001"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000063311.58879.01"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1139-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1855-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15701-2"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.09.019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1254-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.043"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0221-2"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1525-x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4328"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag0481"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411649111"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.11.033"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs152"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhx005"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2020.578483"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12325"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0823-2"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.012587"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.785276"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12236"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00027"},{"key":"e_1_2_9_36_1","article-title":"Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain","author":"Moloney CM","year":"2022","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_37_1","volume-title":"The fine structure of the nervous system: neurons and their supporting cells","author":"Peters A","year":"1991"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01656-x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1364\/OE.21.032306"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000005487"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13118"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom6010009"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36374-4"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.01056"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406109200"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-12679-1_1"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.019265"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt217"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0292-9"},{"key":"e_1_2_9_50_1","article-title":"Hypothesis: tau pathology is an initiating factor in sporadic Alzheimer's disease","author":"Arnsten AFT","year":"2020","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.08.003"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glad134"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.12.001"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18725"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01307-2"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep15709"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.029"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15436-0"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00596-4"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz2387"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.4201"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.12.006"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn960"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00384-3"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.7.2628"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0299-2"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2194"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322360111"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0871-6"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2156-5"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.063"},{"key":"e_1_2_9_72_1","article-title":"Plasma Abeta42\/Abeta40 and phospho\u2010tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease","author":"Rissman RA","year":"2023","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.02.004"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12321"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12892"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208635109"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00380-7"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-014-1315-y"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0227-5"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.13737","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:54:21Z","timestamp":1759935261000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.13737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,6]]},"references-count":78,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/alz.13737"],"URL":"https:\/\/doi.org\/10.1002\/alz.13737","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.07.566046","asserted-by":"object"}]},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,6]]},"assertion":[{"value":"2023-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}