{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:41:41Z","timestamp":1785415301799,"version":"3.56.0"},"reference-count":73,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["P20GM113109"],"award-info":[{"award-number":["P20GM113109"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"award":["P20GM113109"],"award-info":[{"award-number":["P20GM113109"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disease impacting over 6 million Americans, with cases projected to increase to over 14 million by 2060. The AD pathology leads to difficulty completing everyday tasks or conversations, and ultimately, progresses to disrupt the most basic bodily functions and require full-time caretaking. While disease-modifying therapy remains elusive, reducing the incidence of AD is crucial to mitigate the projected increase in cases. Exercise has emerged as an effective strategy to promote brain health in late adulthood and to protect against the onset of AD. Exercise opposes several disease processes, including cognitive dysfunction, amyloid beta aggregation, tau phosphorylation, and deficits in hippocampal volume, mitochondrial function, cerebral blood flow, and neurogenesis, through various pathways, including the systemic release of exerkines. The exerkine irisin is an important mediator of the beneficial relationship between exercise and the brain. Previous work administering irisin therapeutically to healthy and preclinical AD mice has demonstrated irisin use to replicate multiple exercise-induced effects in the brain and protect against AD-induced deficits. Although irisin is suggested as a promising strategy for promoting brain health in late adulthood, our understanding of irisin signaling and its protective effects against AD remains incomplete. This review will investigate irisin as an important, physiologically relevant promoter of brain health in aging and AD.<\/jats:p>","DOI":"10.3390\/biom16050687","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:30:22Z","timestamp":1778059822000},"page":"687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Irisin as an Exerkine of Neuroprotection in Aging and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-6002","authenticated-orcid":false,"given":"Zachary J.","family":"White","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","unstructured":"(2026, April 16). 2025 Alzheimer\u2019s Disease Facts and Figures\u2014PMC, Available online: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC12040760\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1002\/alz.12362","article-title":"Population Estimate of People with Clinical Alzheimer\u2019s Disease and Mild Cognitive Impairment in the United States (2020\u20132060)","volume":"17","author":"Rajan","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1474-4422(18)30028-0","article-title":"Spatial Patterns of Neuroimaging Biomarker Change in Individuals from Families with Autosomal Dominant Alzheimer\u2019s Disease: A Longitudinal Study","volume":"17","author":"Gordon","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1038\/ncomms11934","article-title":"Early Role of Vascular Dysregulation on Late-Onset Alzheimer\u2019s Disease Based on Multifactorial Data-Driven Analysis","volume":"7","author":"Sotero","year":"2016","journal-title":"Nat. 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