{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:30:13Z","timestamp":1785407413672,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,20]]},"group-title":"Neuroscience","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 AG066429"],"award-info":[{"award-number":["R01 AG066429"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AG072719"],"award-info":[{"award-number":["R01 AG072719"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AG067763"],"award-info":[{"award-number":["R01 AG067763"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RF1 AG054199"],"award-info":[{"award-number":["RF1 AG054199"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AG054672"],"award-info":[{"award-number":["R01 AG054672"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/05ewr7t48","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"crossref","award":["ZEN-26-1436830"],"award-info":[{"award-number":["ZEN-26-1436830"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Centre INRAE Grand-Est - Colmar","award":["DIGIT-BIO metaprogram DINAMIC grant"],"award-info":[{"award-number":["DIGIT-BIO metaprogram DINAMIC grant"]}]},{"name":"D\u00e9l\u00e9gation R\u00e9gionale Nouvelle-Aquitaine","award":["CHESS Exomarquage 13059720-13062120"],"award-info":[{"award-number":["CHESS Exomarquage 13059720-13062120"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Tau pathology emerges early in Alzheimer\u2019s disease within entorhinal cortex layer II (ECII) and reaches hippocampal CA1, but how this circuit-level spread translates into sex-dependent vulnerability remains unclear. Using a circuit-defined model in which P301L human tau is expressed selectively in Wolframin-1 (Wfs1\n                  <jats:sup>+<\/jats:sup>\n                  ) ECII neurons and propagates to CA1, we found that the extent and proximal\u2013distal distribution of tau-positive CA1 neurons were comparable in males and females. Despite similar propagation, females exhibited broad hippocampal-dependent cognitive impairment (working memory, object recognition, fear acquisition, trace associative memory, and contextual fear memory), whereas males showed a selective deficit in trace associative memory. Consistent with these behavioral outcomes, CA1 pyramidal neurons in tau-propagated females displayed reduced excitability (slower action potential kinetics, reduced firing during depolarizing steps) and reduced spontaneous excitatory postsynaptic current (EPSC) amplitude, while males showed subtler intrinsic changes with altered EPSC kinetics. Bulk RNA sequencing of entorhinal cortex and CA1 revealed robust immune pathway engagement after tau propagation, with males showing a stronger Th1\/Th2 and neuroinflammatory signature and CTLA4-associated signaling changes, whereas females showed prominent complement\u2013phagosome pathway enrichment and a female-specific increase in Clec7a\n                  <jats:sup>+<\/jats:sup>\n                  microglia density in CA1. CD4\n                  <jats:sup>+<\/jats:sup>\n                  T-cell infiltration into CA1 was detected in both sexes. Together, these results indicate that sex-specific neuroimmune programs, rather than differences in tau propagation load, shape CA1 electrophysiological dysfunction and the breadth of memory impairment following early entorhinal-to-hippocampal tau spread.\n                <\/jats:p>","DOI":"10.64898\/2026.02.19.706636","type":"posted-content","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:05:18Z","timestamp":1771610718000},"source":"Crossref","is-referenced-by-count":0,"title":["Entorhinal Cortex Wolframin-1-expressing neurons propagate tau to CA1 neurons and impair hippocampal memory"],"prefix":"10.64898","author":[{"given":"Jean-Christophe","family":"Delpech","sequence":"first","affiliation":[{"name":"University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, France"},{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinidhi Venkatesan","family":"Kalavai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruba","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun Reddy","family":"Ravula","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL 32224, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heena V.","family":"Lad","sequence":"additional","affiliation":[{"name":"University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 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