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Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease\u2013related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD\/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD\/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.<\/jats:p>","DOI":"10.1093\/infdis\/jiae200","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T17:27:27Z","timestamp":1725989247000},"page":"S141-S149","source":"Crossref","is-referenced-by-count":8,"title":["Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome"],"prefix":"10.1093","volume":"230","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1797-4288","authenticated-orcid":false,"given":"Stephen D","family":"Ginsberg","sequence":"first","affiliation":[{"name":"Center for Dementia Research, Nathan Kline Institute , Orangeburg, New York"},{"name":"Department of Psychiatry"},{"name":"Neuroscience and Physiology"},{"name":"NYU Neuroscience Institute, New York University Grossman School of Medicine , New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J","family":"Blaser","sequence":"additional","affiliation":[{"name":"Center for 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