{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:47:04Z","timestamp":1793141224950,"version":"4.5.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Developing effective treatment for Alzheimer\u2019s disease (AD) remains a challenge. This can be partially attributed to the fact that the mouse models used in preclinical research largely replicate familial form of AD, while majority of human cases are sporadic; both forms differ widely in the onset and origin of pathology, therefore requiring specific\/targeted treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we aimed to model sporadic AD in mice by combining two of the many risk factors that are strongly implicated in AD: ApoE4, a major genetic risk factor, together with an inflammatory stimuli. Accordingly, we subjected ApoE4 knock in (KI) mice, expressing humanized ApoE4, to low doses of Lipopolysaccharide (LPS) injections (i.p, weekly, for 4 months).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We assessed these animals for behavioral impairments at 6 months of age using Open Field, Y-maze, and Barnes Maze Test. LPS induced hypoactivity was observed in the Open Field and Y-maze test, whereas spatial learning and memory was intact. We then quantified differences in dendritic spine density, which is a strong correlate of AD. ApoE4KI mice showed a significant reduction in the number of spines after treatment with LPS, whereas there were no obvious differences in the total number of microglia and astrocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>To conclude, in the current study the APoEe4 risk gene increases the vulnerability of hippocampal neurons to inflammation induced spine loss, laying a foundation for an early sporadic AD mouse model.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2024.1357405","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T04:36:24Z","timestamp":1709008584000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Modeling sporadic Alzheimer\u2019s disease in mice by combining Apolipoprotein E4 risk gene with environmental risk factors"],"prefix":"10.3389","volume":"16","author":[{"given":"Kiruthika","family":"Ganesan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Rentsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Langdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke T.","family":"Milham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce","family":"Vissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/alz.12328","article-title":"2021 Alzheimer's disease facts and figures","volume":"17","year":"2021","journal-title":"Alzheimers Dement."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.5114\/fn.2019.85929","article-title":"Risk factors for Alzheimer\u2019s disease","volume":"57","author":"Armstrong","year":"2019","journal-title":"Folia Neuropathol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1001\/jama.2017.20373","article-title":"Effect of Idalopirdine as adjunct to cholinesterase inhibitors on change in cognition in patients with Alzheimer disease: three randomized clinical trials","volume":"319","author":"Atri","year":"2018","journal-title":"JAMA"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/ctn6030020","article-title":"Effects of different lipopolysaccharide doses on short-and long-term spatial memory and Hippocampus morphology in an experimental Alzheimer&rsquo;s disease model","volume":"6","author":"Bahaidrah","year":"2022","journal-title":"Clin. 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