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Increasing evidence suggests that bile acids, traditionally recognized for their roles in lipid digestion and hepatic metabolism, act as endocrine signaling molecules that influence central nervous system (CNS) homeostasis. Through enterohepatic circulation and microbiota-dependent biotransformation, bile acid composition is dynamically regulated and can modulate peripheral metabolic and immune pathways with downstream effects on the brain. Notably, bile acid signaling via key receptors such as the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 and G-protein-coupled bile acid receptor 1 (TGR5\/GPBAR1) has emerged as a mechanistic bridge linking liver\u2013gut physiology to neuroinflammatory and neurodegenerative processes. Altered bile acid profiles have been reported in AD and mild cognitive impairment, with accumulating findings suggesting that hydrophobic secondary bile acids may contribute to blood\u2013brain barrier (BBB) disruption and neurotoxicity. In contrast, hydrophilic bile acids may exert neuroprotective and anti-inflammatory effects. In addition, bile acids drive the release of gut hormones such as glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), highlighting indirect neurometabolic pathways relevant to cognition and neurodegeneration. This narrative review synthesizes current biochemical, experimental, and clinical evidence supporting a role for bile acid signaling in AD pathogenesis and progression. We discuss receptor-mediated pathways, microbiota-bile acid interactions, neuroimmune modulation, and translational perspectives, proposing that bile acid\u2013based biomarkers and therapeutic strategies targeting FXR\/TGR5 signaling may represent promising avenues for future AD intervention.<\/jats:p>","DOI":"10.1007\/s00210-026-05516-1","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T02:52:29Z","timestamp":1780973549000},"page":"16841-16859","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bile acids in Alzheimer\u2019s disease: a double-edged sword in gut\u2013liver\u2013brain signaling and neurodegeneration"],"prefix":"10.1007","volume":"399","author":[{"given":"Rehana","family":"Basri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayder M.","family":"Al-kuraishy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubarak","family":"Alruwaili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali I.","family":"Al-Gareeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali K.","family":"Albuhadily","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-7236","authenticated-orcid":false,"given":"Athanasios","family":"Alexiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9020-874X","authenticated-orcid":false,"given":"Marios","family":"Papadakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1827-6131","authenticated-orcid":false,"given":"Safaa A.","family":"Faheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7817-425X","authenticated-orcid":false,"given":"Gaber El-Saber","family":"Batiha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"5516_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101556","volume":"75","author":"E Aaldijk","year":"2022","unstructured":"Aaldijk E, Vermeiren Y (2022) The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer\u2019s disease: a narrative review. 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