{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:36Z","timestamp":1792790436959,"version":"4.5.0"},"posted":{"date-parts":[[2026,10,5]]},"group-title":"Animal Behavior and Cognition","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["WE.03-2021-03"],"award-info":[{"award-number":["WE.03-2021-03"]}],"id":[{"id":"https:\/\/ror.org\/03cw2h814","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/04dkp9463","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/01yaj9a77","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Netherlands Institute for Neuroscience","id":[{"id":"https:\/\/ror.org\/05csn2x06","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03ey3qt70","id-type":"ROR","asserted-by":"publisher"}]},{"name":"French National Research Agency","id":[{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"French Ministry of Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Cognitive resilience to Alzheimer\u2019s disease (AD) can be modelled in amyloid-expressing rodents through early handling (EH). This study investigated how EH and sex affect cognition and pathology over time.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We assessed cognition (open field, object recognition test, Barnes maze) in 6- and 12-month-old APP\/PS1 and WT mice (N=180, EH\/Ctrl\u00d7M\/F), performed biochemical and histological analyses of several brain areas to assess effects on A\u03b2, glial cells, and other markers of pathology, and investigated how behavior correlates with pathology.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>EH improved non-spatial memory at 6 months, consistent with a reduction of hippocampal microglia density, and normalized locomotor activity at 12 months (both p&lt;0.05). Females demonstrated similar (6 &amp; 12 months) or better (12 months) cognition, despite greater pathology across timepoints. Correlations implicated microglial recruitment in EH-related effects, supported by morphological analysis of prefrontal regions (p&lt;0.05).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSION<\/jats:title>\n                  <jats:p>Our findings highlight the critical role of early postnatal experiences and sex in shaping resilience in the context of AD pathology.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.29.754953","type":"posted-content","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:10:23Z","timestamp":1791234623000},"source":"Crossref","is-referenced-by-count":0,"title":["The modulatory role of early-life experiences and sex on cognitive resilience in APP\/PS1 mice over time"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3506-9708","authenticated-orcid":false,"given":"Maria","family":"Carrigan","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands"},{"name":"Brain Plasticity Group, Swammerdam Institute, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9248-8255","authenticated-orcid":false,"given":"Jeniffer","family":"Sanguino-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melis","family":"Bayer-Var","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Minko","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alise","family":"Bobkova","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Ruzicka","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"L\u00f3pez-Fedjajeva","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute, University of Amsterdam, Amsterdam, The 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