{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:40:10Z","timestamp":1789749610854,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T00:00:00Z","timestamp":1685145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 BX004146"],"award-info":[{"award-number":["I01 BX004146"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["AARGD-17-505409"],"award-info":[{"award-number":["AARGD-17-505409"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","award":["I01 BX004146"],"award-info":[{"award-number":["I01 BX004146"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","award":["AARGD-17-505409"],"award-info":[{"award-number":["AARGD-17-505409"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UMN Healthy Foods, Healthy Lives Institute","award":["I01 BX004146"],"award-info":[{"award-number":["I01 BX004146"]}]},{"name":"UMN Healthy Foods, Healthy Lives Institute","award":["AARGD-17-505409"],"award-info":[{"award-number":["AARGD-17-505409"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Obesity, a known risk factor of Alzheimer\u2019s disease (AD), increases the activation of microglia, leading to a proinflammatory phenotype. Our previous work shows that a high fat diet (HFD) can cause neuroinflammation and cognitive decline in mice. We hypothesized that proinflammatory activation of brain microglia in obesity exacerbates AD pathology and increases the accumulation of amyloid beta (A\u03b2) plaques. Presently, we tested cognitive function in 8-month-old male and female APP\/PS1 mice fed a HFD, starting at 1.5 months of age. Locomotor activity, anxiety-like behavior, behavioral despair, and spatial memory were all assessed through behavioral tests. Microgliosis and A\u03b2 deposition were measured in multiple brain regions through immunohistochemical analysis. Our results show that a HFD decreases locomotor activity, while increasing anxiety-like behavior and behavioral despair independent of genotype. A HFD led to increased memory deficits in both sexes, with HFD-fed APP\/PS1 mice performing the worst out of all groups. Immunohistochemical analysis showed increased microgliosis in mice fed a HFD. This was accompanied by an increase in A\u03b2 deposition in the HFD-fed APP\/PS1 mice. Together, our results support that HFD-induced obesity exacerbates neuroinflammation and A\u03b2 deposition in a young adult AD mouse model, leading to increased memory deficits and cognitive decline in both sexes.<\/jats:p>","DOI":"10.3390\/nu15112494","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:16:04Z","timestamp":1685204164000},"page":"2494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Early Life Obesity Increases Neuroinflammation, Amyloid Beta Deposition, and Cognitive Decline in a Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-073X","authenticated-orcid":false,"given":"Simon W.","family":"So","sequence":"first","affiliation":[{"name":"Minneapolis Veterans Affairs Health Care System, Minneapolis, MN 55417, USA"},{"name":"Department of Neuroscience, University of Minnesota Twin Cities, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra M.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Minneapolis Veterans Affairs Health Care System, Minneapolis, MN 55417, USA"},{"name":"Department of Neuroscience, University of Minnesota Twin Cities, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Nixon","sequence":"additional","affiliation":[{"name":"Minneapolis Veterans Affairs Health Care System, Minneapolis, MN 55417, USA"},{"name":"Department of Food Science and Nutrition, University of Minnesota Twin Cities, St. Paul, MN 55108, USA"},{"name":"Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy A.","family":"Butterick","sequence":"additional","affiliation":[{"name":"Minneapolis Veterans Affairs Health Care System, Minneapolis, MN 55417, USA"},{"name":"Department of Neuroscience, University of Minnesota Twin Cities, Minneapolis, MN 55455, USA"},{"name":"Department of Food Science and Nutrition, University of Minnesota Twin Cities, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/mp.2015.129","article-title":"Midlife adiposity predicts earlier onset of Alzheimer\u2019s dementia, neuropathology and presymptomatic cerebral amyloid accumulation","volume":"21","author":"Chuang","year":"2016","journal-title":"Mol. 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