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Contextual fear memory was used as a continuous measure of cognitive function. Pseudobulk differential expression analyses identified transcriptional changes associated with aging and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Aging and cognitive decline exhibited differential transcriptional signatures. Aging\u2010related changes were modest and cell\u2010type specific, with early responses in excitatory neurons followed by increased glial remodeling. Conversely,\u00a0cognitive decline was associated with widespread transcriptional alterations predominantly in excitatory neurons, enriched for proteostasis and glutathione\/redox pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings indicate that cognitive decline is not simply a consequence of aging but reflects distinct molecular processes in excitatory neurons. Proteostasis and redox pathways may represent conserved mechanisms supporting cognitive resilience.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71825","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:41:15Z","timestamp":1789620075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hippocampal snRNA\u2010seq in Collaborative Cross reveals molecular signatures of cognitive resilience independent of chronological aging"],"prefix":"10.1002","volume":"22","author":[{"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Ouellette","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"},{"name":"University of Louisville  Louisville Kentucky 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