{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T07:20:35Z","timestamp":1773213635026,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,5]]},"group-title":"Neuroscience","reference-count":22,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AG067971"],"award-info":[{"award-number":["AG067971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AG081632"],"award-info":[{"award-number":["AG081632"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AG090275"],"award-info":[{"award-number":["AG090275"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Center for Synthetic Immunity, the Geisel School of Medicine at Dartmouth"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract\/Summary<\/jats:title>\n                <jats:p>Cellular therapies are one class of medicine being developed to treat Alzheimer\u2019s disease (AD), a neurodegenerative disease with memory loss, aberrant protein accumulation in the brain, and neuroinflammation. One challenge for development of human cell therapeutics is to have preclinical animal models that allow the use of human cells without immune-mediated rejection of those cells. The 5xFAD transgenic mouse model is a robust disease model for AD that expresses human amyloid precursor protein and presenilin-1 with multiple familial AD mutations, develops microglia-mediated neuroinflammation, accumulates amyloid-beta (A\u03b2) in the brain, and shows behavior changes with age. To create a mouse model for AD that permits the transplantation of human cells without immune-mediated rejection, we bred the 5xFAD transgenes onto the NOD-SCID-IL-2R\u03b3-deficient (NSG) mouse model to create 5xFAD-NSG mice. We report that 5xFAD-NSG mice develop A\u03b2 plaques in the brain, microgliosis, neuroinflammation, and behavior changes that increase with age. We demonstrate that injection of CAR engineered human T regulatory cells are detected in the cerebral cortex and spleen after eight days. This 5xFAD-NSG mouse model for AD will be helpful to develop human cell-based therapies for AD.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>\n                    5xFAD transgenic NSG mice develop a progressive AD-like disease and are an\n                    <jats:italic>in vivo<\/jats:italic>\n                    model for testing human cell-based therapies for AD.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.03.709048","type":"posted-content","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:25:24Z","timestamp":1772774724000},"source":"Crossref","is-referenced-by-count":0,"title":["5xFAD-NSG mice: a preclinical Alzheimer model for human cell therapy studies"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2982-2522","authenticated-orcid":false,"given":"David J","family":"Graber","sequence":"first","affiliation":[{"name":"Center for Synthetic Immunity, Department of Microbiology and Immunology, the Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Louise","family":"Sentman","sequence":"additional","affiliation":[{"name":"Center for Synthetic Immunity, Department of Microbiology and Immunology, the Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. James","family":"Cook","sequence":"additional","affiliation":[{"name":"Center for Synthetic Immunity, Department of Microbiology and Immunology, the Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-5847","authenticated-orcid":false,"given":"Charles L","family":"Sentman","sequence":"additional","affiliation":[{"name":"Center for Synthetic Immunity, Department of Microbiology and Immunology, the Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"3","key":"2026031002300530000_2026.03.03.709048v1.1","first-page":"792","article-title":"An early and late peak in microglial activation in Alzheimer\u2019s disease trajectory","volume":"140","year":"2017","journal-title":"Brain"},{"issue":"3","key":"2026031002300530000_2026.03.03.709048v1.2","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1177\/03009858231151403","article-title":"Spontaneous early-onset neurodegeneration in the brainstem and spinal cord of NSG, NOG, and NXG mice","volume":"60","year":"2023","journal-title":"Veterinary Pathology"},{"issue":"1","key":"2026031002300530000_2026.03.03.709048v1.3","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41597-021-01054-y","article-title":"Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"8","year":"2021","journal-title":"Scientific Data"},{"key":"2026031002300530000_2026.03.03.709048v1.4","doi-asserted-by":"publisher","DOI":"10.3390\/cells14171318"},{"key":"2026031002300530000_2026.03.03.709048v1.5","doi-asserted-by":"crossref","unstructured":"Graber, D. 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