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How distinct tau forms influence synaptic excitability across brain regions with differing susceptibility to tau accumulation remains unclear. Primary age-related tauopathy (PART), defined by hippocampal-restricted tau pathology in the absence of amyloid-\u03b2, offers a tractable model to investigate tau-specific effects on synaptic physiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine how regionally enriched tau species in PART relate to synaptic excitation\u2013inhibition balance and to identify molecular pathways linking tau oligomers to synaptic dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Autopsy-derived hippocampal and superior middle temporal gyrus tissues from neuropathologically validated PART specimens were analyzed. Tau species, including monomers, oligomers, and paired helical filaments (PHFs), were quantified by western blot. Synaptic function was assessed by microtransplantation of synaptosomal membranes into\n                      <jats:italic toggle=\"yes\">Xenopus laevis<\/jats:italic>\n                      oocytes, followed by electrophysiological recordings of glutamatergic (kainate-evoked AMPAR) and GABAergic (GABA\n                      <jats:sub>A<\/jats:sub>\n                      R) currents to calculate the synaptic excitation-to-inhibition (sE\/I) ratio. Proteomic and enrichment analyses of brain-derived tau oligomer (BDTO) interactomes from PART hippocampi were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PART specimens showed hippocampal accumulation of aggregation-prone tau assemblies (oligomeric and PHF-tau) that were negatively correlated with sE\/I. Proteins within the BDTO interactome linked to reduced sE\/I were enriched for pathways related to vesicle-mediated transport, synaptic endocytosis, and neurotransmitter receptor regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In PART, oligomeric and fibrillar tau are associated with shift toward synaptic inhibition, predominantly within the hippocampus. Proteomic correlates implicate vesicle trafficking pathways as mediators of tau oligomer-associated alterations in synaptic function, providing mechanistic insight into early-stage tauopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261416524","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T13:37:12Z","timestamp":1770644232000},"page":"649-665","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Regional correlates of tau pathology and synaptic function in primary age-related tauopathy"],"prefix":"10.1177","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8427-4837","authenticated-orcid":false,"given":"Shrinath","family":"Kadamangudi","sequence":"first","affiliation":[{"name":"Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5777-6588","authenticated-orcid":false,"given":"Laura","family":"Sanchez-Sanchez","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agenor","family":"Limon","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA"},{"name":"Moody Brain Health Institute, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-447X","authenticated-orcid":false,"given":"Giulio","family":"Taglialatela","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA"},{"name":"Moody Brain Health Institute, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1707-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2015.1"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2194"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012936"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.09.019"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx243"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201457"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31825018f7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw026"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15701-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.043"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.04.020"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28896-3"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071743"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02839-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2023.1129036"},{"key":"e_1_3_3_19_2","first-page":"146","article-title":"Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer\u2019s disease","volume":"2","author":"Tai H-C","year":"2014","unstructured":"Tai H-C, Wang BY, Serrano-Pozo A, et al. 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