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The correlation between Ad and microbial dysbiosis has been repeatedly shown, yet the etiologic cause of microbial dysbiosis remains elusive. From a neuropathology perspective, abnormal (often age-related) changes in the brain, associated structures, and bodily lumens tend toward an accumulation of oxygen-depleted pathologic structures, which are anaerobically selective niches. These anaerobic environments may promote progressive change in the microbial community proximal to the brain and thus deserve further investigation. In this review, we identify and explore what is known about the anaerobic niche near or associated with the brain and the anaerobes that it is harbors. We identify the anaerobe stakeholders within microbiome communities and the impacts on the neurodegenerative processes associated with Ad. Chronic oral dysbiosis in anaerobic dental pockets and the composition of the gut microbiota from fecal stool are the 2 largest anaerobic niche sources of bacterial transference to the brain. At the blood-brain barrier, cerebral atherosclerotic plaques are predominated by anaerobic species intimately associated with the brain vasculature. Focal cerebritis\/brain abscess and corpora amylacea may also establish chronic anaerobic niches in direct proximity to brain parenchyma. In exploring the anaerobic niche proximal to the brain, we identify research opportunities to explore potential sources of microbial dysbiosis associated with Ad.<\/jats:p>","DOI":"10.1093\/infdis\/jiae312","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T20:40:13Z","timestamp":1718224813000},"page":"S117-S127","source":"Crossref","is-referenced-by-count":4,"title":["Unveiling the Intricate Link Between Anaerobe Niche and Alzheimer Disease Pathogenesis"],"prefix":"10.1093","volume":"230","author":[{"given":"NyEmma","family":"Drakes","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical University of South Carolina"},{"name":"Department of Biology, College of Charleston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Kondrikova","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical University of South Carolina"},{"name":"Department of Veterans Affairs, Ralph H. Johnson VA Medical Center , Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Pytel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical University of South Carolina"},{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-7949","authenticated-orcid":false,"given":"Eric D","family":"Hamlett","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"2024091017261052700_jiae312-B1","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.cmi.2019.04.028","article-title":"Contaminating viral sequences in 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