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Here, we demonstrate that PARIS also contributes to Alzheimer\u2019s disease by elevating\n                  <jats:italic>STAT3<\/jats:italic>\n                  transcriptional activity, thereby inducing tau pathology, hippocampal atrophy, and glial activation. Genetic depletion of\n                  <jats:italic>Paris<\/jats:italic>\n                  reduced tau phosphorylation and cognitive decline in tauopathy mice, whereas neuron-specific PARIS overexpression caused tau accumulation, gliosis, and memory impairment. In contrast, astrocyte-specific overexpression did not induce pathology, indicating that PARIS acts in neurons to drive tau phosphorylation and glial activation. The pathological features induced by neuronal PARIS overexpression were rescued by STAT3 inhibition, demonstrating that PARIS\u2013STAT3 signaling underlies these effects. Moreover,\n                  <jats:italic>Paris<\/jats:italic>\n                  knockout did not alter pathology in the amyloid-driven mouse model, highlighting specificity for tau pathology. Together, these findings reveal PARIS as a neuronal regulator of STAT3 signaling that exacerbates tau-mediated neurodegeneration and identify the PARIS\u2013STAT3 pathway as a potential therapeutic target in Alzheimer\u2019s disease.\n                <\/jats:p>","DOI":"10.64898\/2025.12.06.692741","type":"posted-content","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:20:14Z","timestamp":1765380014000},"source":"Crossref","is-referenced-by-count":0,"title":["Neuronal PARIS-STAT3 axis drives tau pathology and glial activation in Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-8277","authenticated-orcid":false,"given":"Ji-Yang","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Akkentli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejin","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhee","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinwon","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Redding-Ochoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Troncoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Ung","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valina L.","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-0893","authenticated-orcid":false,"given":"Ted M.","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025121204250406000_2025.12.06.692741v1.1","first-page":"1474043","article-title":"Alzheimer\u2019s disease: a comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges","volume":"11","year":"2024","journal-title":"Front. 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