{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:59:59Z","timestamp":1788566399318,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R03AG065970"],"award-info":[{"award-number":["R03AG065970"]}]},{"name":"National Institute of Health","award":["P20GM113109"],"award-info":[{"award-number":["P20GM113109"]}]},{"name":"National Institute of Health","award":["2R15AG042781-03"],"award-info":[{"award-number":["2R15AG042781-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the third leading cause of death among older adults with nearly 6 million diagnosed annually. In the race for a cure, one thing is certain\u2014exercise can reduce your risk. However, the mechanisms responsible for this reduced risk are unknown. Several studies have linked exercise to improved memory, reduced amyloid beta plaques, and tau hyperphosphorylation in AD. Background\/Objectives: By utilizing a novel rat model of AD, TgF344-AD, we evaluated the time course of behavioral shifts as well as the protective effect of exercise. Methods: TgF344-AD animals (61 total, 31 females and 30 males) were assessed every 3 months from 3 to 12 months of age and then assessments were increased to monthly until they reached 18 months of age. A progressive treadmill protocol was administered at 12 months of age and continued until 18 months. Pre-intervention and post-intervention data were analyzed. Results: Females had greater grip strength relative to body mass compared to males and exercise attenuated the age-related and AD-induced decline. Also, female AD-impaired memory was rescued with exercise, while males had no exercise-induced improvements. Conclusions: There is a sex difference present in the TgF344-AD rat model of Alzheimer\u2019s disease and this should be studied further; in addition, sex differences across all models of AD and the human pathology need to be evaluated. Exercise neuroprotection, while more prominent in females, is an important factor in AD research, and further work to understand the mechanisms of neuroprotection is warranted.<\/jats:p>","DOI":"10.3390\/brainsci15060631","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T03:59:17Z","timestamp":1749700757000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exercise Improves Alzheimer\u2019s Disease Phenotype in the TgF344-AD Rat, a Behavioral Time Course Study of Males and Females"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-8475","authenticated-orcid":false,"given":"Stephanie E.","family":"Hall","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, 1600 Denison Ave., Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-6002","authenticated-orcid":false,"given":"Zachary J.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, 1600 Denison Ave., Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-1956","authenticated-orcid":false,"given":"Troy T.","family":"Rohn","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Arts and Sciences, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshari H.","family":"Sudasinghe","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, 1600 Denison Ave., Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1493-9548","authenticated-orcid":false,"given":"Michael E.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Psychological Sciences, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/alz.12694","article-title":"Global Estimates on the Number of Persons across the Alzheimer\u2019s Disease Continuum","volume":"19","author":"Gustavsson","year":"2023","journal-title":"Alzheimers Dement. 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