{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:37:55Z","timestamp":1791959875064,"version":"4.3.4"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Phosphorylated tau (p\u2010tau) pathology correlates strongly with cognitive decline and is a pathological hallmark of Alzheimer's Disease (AD). In recent years, phosphorylated transactive response DNA\u2010binding protein (pTDP\u201043) has emerged as a common comorbidity, found in up to 70% of all AD cases (Josephs et al., Acta Neuropathol, 131(4), 571\u2013585; Josephs, Whitwell, et al., Acta Neuropathol, 127(6), 811\u2013824). Current staging schemes for pTDP\u201043 in AD and primary age\u2010related tauopathy (PART) track its progression throughout the brain, but the distribution of pTDP\u201043 within the entorhinal cortex (EC) at the earliest stages has not been studied. Moreover, the exact nature of p\u2010tau and pTDP\u201043 co\u2010localization is debated. We investigated the selective vulnerability of the entorhinal subfields to phosphorylated pTDP\u201043 pathology in preclinical AD and PART postmortem tissue. Within the EC, posterior\u2010lateral subfields showed the highest semi\u2010quantitative pTDP\u201043 density scores, while the anterior\u2010medial subfields had the lowest. On the rostrocaudal axis, pTDP\u201043 scores were higher posteriorly than anteriorly (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.010), peaking at the posterior\u2010most level (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.050). Further, we showed the relationship between pTDP\u201043 and p\u2010tau in these regions at pathology\u2010positive but clinically silent stages. P\u2010tau and pTDP\u201043 presented a similar pattern of affected subregions (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) but differed in density magnitude (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). P\u2010tau burden was consistently higher than pTDP\u201043 at every anterior\u2013posterior level and in most EC subfields. These findings highlight pTDP\u201043 burden heterogeneity within the EC and the posterior\u2010lateral subfields as the most vulnerable regions within stage II of the current pTDP\u201043 staging schemes for AD and PART. The EC is a point of convergence for p\u2010tau and pTDP\u201043 and identifying its most vulnerable neuronal populations will prove key for early diagnosis and disease intervention.\n                  <\/jats:p>","DOI":"10.1111\/bpa.13159","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T18:24:13Z","timestamp":1681151053000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<scp>TDP<\/scp>\n                    \u201043 and tau concurrence in the entorhinal subfields in primary\n                    <scp>age\u2010related<\/scp>\n                    tauopathy and preclinical Alzheimer's disease"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5532-7786","authenticated-orcid":false,"given":"Josu\u00e9","family":"Llamas\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Oltmer","sequence":"additional","affiliation":[{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Champion","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Frosch","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-6671","authenticated-orcid":false,"given":"Jean C.","family":"Augustinack","sequence":"additional","affiliation":[{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.10.093"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1134108"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410106"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1791"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12618"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12430"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0480-1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30284-3"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1537-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1269-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00503-x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1110-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.254"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.10.003"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab099"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz099"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab092"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1679-9"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0845-8"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.060438"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-33"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1951-7"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21425"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-00934-5"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-018-0300-0"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02295-2"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1380-1"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1211-9"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215567"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac074"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903550203"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12321"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1349-0"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02197-9"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01275-7"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0929-5"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.09.048"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00764-7"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab114"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12068"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3606"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.01.016"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12206"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlaa029"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.1099"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254357"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2013.06.033"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx175"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21154"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0408-9"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009058"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70156-9"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01309-6"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002375"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlz005"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004891"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.13159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T20:39:20Z","timestamp":1721075960000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.13159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,10]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/bpa.13159"],"URL":"https:\/\/doi.org\/10.1111\/bpa.13159","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,10]]},"assertion":[{"value":"2023-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13159"}}