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AD pathology is characterized by senile plaques and neurofibrillary tangles (NFTs) composed of amyloid\u2010\u03b2 (A\u03b2) and hyperphosphorylated tau, respectively. Neuroinflammation has been shown to drive A\u03b2 and tau pathology, with evidence suggesting the nod\u2010like receptor family pyrin domain containing 3 (NLRP3) inflammasome as a key pathway in AD pathogenesis. NLRP3 inflammasome activation in microglia, the primary immune effector cells of the brain, results in caspase\u20101 activation and secretion of IL\u20101\u03b2 and IL\u201018. Recent studies have demonstrated a dramatic interplay between the metabolic state and effector functions of immune cells. Microglial metabolism in AD is of particular interest, as ketone bodies (acetone, acetoacetate (AcAc), and \u03b2\u2010hydroxybutyrate (BHB)) serve as an alternative energy source when glucose utilization is compromised in the brain of patients with AD. Furthermore, reduced cerebral glucose metabolism concomitant with increased BHB levels has been demonstrated to inhibit NLRP3 inflammasome activation. Here, we review the role of the NLRP3 inflammasome and microglial ketone body metabolism in AD pathogenesis. We also highlight NLRP3 inflammasome inhibition by several ketone body therapies as a promising new treatment strategy for AD.<\/jats:p>","DOI":"10.1111\/imr.13365","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T09:33:13Z","timestamp":1720690393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Ketone body metabolism and the <scp>NLRP3<\/scp> inflammasome in Alzheimer's disease"],"prefix":"10.1111","volume":"329","author":[{"given":"Daniel C.","family":"Shippy","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine and Public Health University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail H.","family":"Evered","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine and Public Health University of 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