{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:24:36Z","timestamp":1792016676441,"version":"4.4.0"},"reference-count":149,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"McMaster Institute for Research in Aging (MIRA)","award":["PJT-159493"],"award-info":[{"award-number":["PJT-159493"]}]},{"name":"McMaster Institute for Research in Aging (MIRA)","award":["PJT 190135"],"award-info":[{"award-number":["PJT 190135"]}]},{"name":"McMaster Institute for Research in Aging (MIRA)","award":["RGPIN-2022-05192"],"award-info":[{"award-number":["RGPIN-2022-05192"]}]},{"name":"Canadian Institutes of Health Research","award":["PJT-159493"],"award-info":[{"award-number":["PJT-159493"]}]},{"name":"Canadian Institutes of Health Research","award":["PJT 190135"],"award-info":[{"award-number":["PJT 190135"]}]},{"name":"Canadian Institutes of Health Research","award":["RGPIN-2022-05192"],"award-info":[{"award-number":["RGPIN-2022-05192"]}]},{"name":"Canadian Consortium on Neurodegeneration in Aging","award":["PJT-159493"],"award-info":[{"award-number":["PJT-159493"]}]},{"name":"Canadian Consortium on Neurodegeneration in Aging","award":["PJT 190135"],"award-info":[{"award-number":["PJT 190135"]}]},{"name":"Canadian Consortium on Neurodegeneration in Aging","award":["RGPIN-2022-05192"],"award-info":[{"award-number":["RGPIN-2022-05192"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada","award":["PJT-159493"],"award-info":[{"award-number":["PJT-159493"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada","award":["PJT 190135"],"award-info":[{"award-number":["PJT 190135"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada","award":["RGPIN-2022-05192"],"award-info":[{"award-number":["RGPIN-2022-05192"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer\u2019s disease (AD). Extracellular aggregates of amyloid-\u03b2 (A\u03b2) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in the AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated A\u03b2 and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on the mechanisms behind exercise-induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer\u2019s disease pathology. Exercise releases into the circulation a host of hormones and factors from a variety of peripheral tissues. Mechanisms of BDNF induction discussed here are osteocalcin, FNDC5\/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are not yet fully understood but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline.<\/jats:p>","DOI":"10.3390\/biom13111577","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T02:40:07Z","timestamp":1698288007000},"page":"1577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Sama","family":"Jaberi","sequence":"first","affiliation":[{"name":"Graduate Program in Neuroscience, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6815-0529","authenticated-orcid":false,"given":"Margaret","family":"Fahnestock","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). 2023 Alzheimer\u2019s Disease Facts and Figures. 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