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The mammalian\/mechanistic target of rapamycin (mTOR) pathway has emerged as a key driver of AD-related vascular dysfunction. Consistent with this role, attenuation of mTOR signaling restores multiple aspects of cerebrovascular function in AD models, including vascular density, cerebral blood flow, vascular reactivity, and neurovascular coupling. However, the molecular mechanisms linking mTOR dysregulation to cerebrovascular dysfunction in AD remain poorly understood we assessed cerebrovascular levels of RNA-regulatory proteins in hAPP(J20) mice treated with rapamycin from 6 to 12 months of age. Rapamycin partially restored disease-suppressed heterogeneous nuclear ribonucleoprotein (hnRNP) family members, including hnRNP D1 (AUF1) and hnRNP E1 (PCBP1). Rapamycin-mediated restoration of hnRNP extended to the cerebrovasculature of PS19 (P301S) tauopathy mice, indicating that mTOR-dependent hnRNP suppression is shared across amyloid- and tau-driven models of AD. Consistent with these findings, hnRNP E1 and hnRNP L each showed a nominally significant inverse relationship with Braak stage in AD patient brains, with a similar but non-significant trend for hnRNP R and hnRNP M; The coordinated pattern of decline suggests network-level disruption of RNA-binding protein homeostasis in AD. Together, our studies uncover a previously unrecognized link between mTOR signaling and the regulation of RNA-regulatory proteins and identify a previously unrecognized, reversible mTOR-dependent RNA regulatory program in the cerebrovasculature that may contribute to neurovascular dysfunction in AD and reveal new targets for therapeutic intervention.<\/jats:p>","DOI":"10.64898\/2026.09.15.750223","type":"posted-content","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:05:16Z","timestamp":1789556716000},"source":"Crossref","is-referenced-by-count":0,"title":["mTOR disrupts cerebrovascular RNA regulatory networks in Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2118-7555","authenticated-orcid":false,"given":"Haneen","family":"Makhlouf","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, 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