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The molecular basis of this cognitive resilience remains poorly understood due to a lack of mechanistic models. Here, we integrate systems-level Boolean network modeling with\n                  <jats:italic>in vivo<\/jats:italic>\n                  validation to define the transcriptomic logic of AsymAD and uncover a novel preclinical model. Using Boolean implication networks trained on large-scale human cortical RNA-seq datasets, we identified a robust and invariant AD gene signature that accurately stratifies disease states across independent datasets. Application of this signature to Chromogranin A\u2013 deficient PS19 mice (CgA-KO\/PS19) revealed a unique resilience phenotype: male mice developed AD-like molecular and neuropathological profiles in the pre-frontal cortex yet retained intact learning and memory. Female CgA-KO\/PS19 mice displayed even greater protection, including reduced Tau phosphorylation and preserved synaptic ultrastructure. These findings establish the first validated murine model of AsymAD and identify CgA as a modifiable node linking neuroendocrine signaling, Tauopathy, and cognitive preservation. This work provides a scalable platform to probe sex-specific resilience, uncover early-stage biomarkers, and accelerate preventive therapeutic development in AD.\n                <\/jats:p>","DOI":"10.1101\/2025.06.11.659207","type":"posted-content","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T12:45:16Z","timestamp":1749818716000},"source":"Crossref","is-referenced-by-count":0,"title":["Boolean Network Modeling Identifies Cognitive Resilience in the First Murine Model of Asymptomatic Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"given":"Suborno","family":"Jati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Taheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satadeepa","family":"Kal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-5677","authenticated-orcid":false,"given":"Subhash C.","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Head","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8300-9873","authenticated-orcid":false,"given":"Sushil 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