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While cirrhosis is associated with cognitive impairment, its underlying mechanisms remain poorly understood. This study aimed to assess the presence of central nervous system (CNS) markers of Alzheimer\u2019s disease in a rat model of chronic liver disease. Standard histochemical techniques were employed, including Congo red staining for amyloid-\u03b2 (A\u03b2) and Gallyas silver staining for tau pathology. Immunohistochemistry was used to evaluate changes in aquaporin (Aqp1, Aqp4, Aqp9) expression and astrocytic glial fibrillary acidic protein (GFAP) levels. Furthermore, blood concentrations of neurodegeneration markers, neurofilament light chain (NfL), A\u03b2, phosphorylated tau (p-tau), total tau (t-tau), GFAP, and myelin oligodendrocyte glycoprotein (MOG), along with bile acids, were quantified and compared between BDL and SHAM control groups to investigate potential systemic correlates of CNS pathology. CNS analysis revealed the presence of intracellular amyloid-\u03b2 (iA\u03b2) and abnormal tau aggregates (pre-tangle\/tangle stages), consistent with early AD pathology. Additionally, alterations in aquaporin water channels and astrocytic GFAP expression were observed. Peripheral blood analysis showed significant changes in neurodegeneration markers (NfL, A\u03b2, p-tau, t-tau, GFAP, MOG) and bile acid profiles, reinforcing the systemic nature of neuroinflammatory processes in liver disease. Our findings emphasize liver failure as a significant factor in cognitive decline and increased AD risk. The study advocates for incorporating liver function screening into the diagnostic workup of patients with dementia.<\/jats:p>","DOI":"10.1038\/s41598-025-21054-x","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:12:45Z","timestamp":1761829965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Liver dysfunction triggers early Alzheimer\u2019s pathology in an adult rat model of chronic liver disease"],"prefix":"10.1038","volume":"15","author":[{"given":"O.","family":"Braissant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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