{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:40Z","timestamp":1780333900885,"version":"3.54.1"},"reference-count":21,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,2,14]]},"abstract":"<jats:p>In this commentary, we offer an overview of the several environmental and metabolic factors that have been identified as contributing to the development of Alzheimer\u2019s disease (AD). Many of these factors involve extracranial organ systems including immune system dysfunction accompanied by neuroinflammation (inflammaging), gastrointestinal dysbiosis, insulin resistance, and hepatic dysfunction. A variety of microbial factors including mouth flora, viruses, and fungi appear to play a significant role. There is a role for the colonic microbiome becoming dysbiotic and producing toxic metabolites. Declining hepatic function contributes diminished neuronal precursors and reduces toxin elimination. Environmental toxins especially metals play an important role in impairing the blood-brain barrier and acting synergistically with biotoxins and other toxic chemicals. Prevention and treatment of AD appears to require measuring several of these biomarkers and implementing corrective actions regarding such toxicants and correcting metabolic dysfunction at early or preclinical stages of this disorder.<\/jats:p>","DOI":"10.3233\/jad-221078","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T13:03:52Z","timestamp":1672751032000},"page":"1277-1281","source":"Crossref","is-referenced-by-count":14,"title":["Alzheimer\u2019s Disease Is a Multi-Organ Disorder: It May Already Be Preventable"],"prefix":"10.1177","volume":"91","author":[{"given":"Arnold R.","family":"Eiser","sequence":"first","affiliation":[{"name":"Penn Center for Public Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Environmental Neuroscience Group, Center for Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Fulop","sequence":"additional","affiliation":[{"name":"Center on Aging, University of Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-221078_ref1","doi-asserted-by":"crossref","first-page":"147076","DOI":"10.1016\/j.brainres.2020.147076","article-title":"Extra-cranial factors in the development of Alzheimer\u2019s disease","volume":"1748","author":"Eiser","year":"2020","journal-title":"Brain Res"},{"key":"10.3233\/JAD-221078_ref2","doi-asserted-by":"crossref","first-page":"9207","DOI":"10.3390\/ijms22179207","article-title":"Tau protein interaction partners and their roles in Alzheimer\u2019s disease and other tauopathies","volume":"22","author":"Sinsky","year":"2021","journal-title":"Int Mol Sci"},{"key":"10.3233\/JAD-221078_ref3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1212\/WNL.0000000000006926","article-title":"Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases","volume":"92","author":"Espay","year":"2019","journal-title":"Neurology"},{"key":"10.3233\/JAD-221078_ref4","doi-asserted-by":"crossref","first-page":"425","DOI":"10.12688\/f1000research.50786.1","article-title":"Epidemiology of Alzheimer\u2019s disease and other dementias: Rising global burden and forecasted trends","volume":"10","author":"Javaid","year":"2021","journal-title":"F1000Research"},{"key":"10.3233\/JAD-221078_ref5","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.3233\/JAD-171133","article-title":"Alzheimer\u2019s Amyloid-\u03b2 is an antimicrobial peptide: A review of the evidence","volume":"62","author":"Gosztyla","year":"2018","journal-title":"J Alzheimers Dis"},{"issue":"Suppl 1","key":"10.3233\/JAD-221078_ref6","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.3233\/JAD-221078_ref7","doi-asserted-by":"crossref","first-page":"116","DOI":"10.2174\/1567205012666150204121719","article-title":"Role of environmental contaminants in the etiology of Alzheimer\u2019s disease: A review","volume":"12","author":"Yegambaram","year":"2015","journal-title":"Curr Alzheimer Res"},{"key":"10.3233\/JAD-221078_ref8","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1474-4422(20)30231-3","article-title":"Insulin resistance in Alzheimer\u2019s disease and related disorders: Mechanisms and therapeutic approaches","volume":"19","author":"Kellar","year":"2020","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-221078_ref9","doi-asserted-by":"crossref","first-page":"6695796","DOI":"10.1155\/2021\/6695796","article-title":"Connection between the altered HDL antioxidant and anti-inflammatory properties and the risk to develop Alzheimer\u2019s disease: A narrative review","volume":"2021","author":"Zimetti","year":"2021","journal-title":"Oxid Med Cell Longev"},{"key":"10.3233\/JAD-221078_ref10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.3233\/JAD-160152","article-title":"Microbes and Alzheimer\u2019s disease","volume":"51","author":"Itzhaki","year":"2016","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-221078_ref11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fneur.2014.00043","article-title":"The gastrointestinal tract microbiome and potential link to Alzheimer\u2019s disease","volume":"5","author":"Hill","year":"2014","journal-title":"Front Neurol"},{"key":"10.3233\/JAD-221078_ref12","doi-asserted-by":"crossref","first-page":"8088","DOI":"10.1038\/s41598-020-65196-6","article-title":"Relationship between dementia and gut microbiome-associated metabolites: A cross-sectional study in Japan","volume":"10","author":"Saji","year":"2020","journal-title":"Sci Rep"},{"key":"10.3233\/JAD-221078_ref13","doi-asserted-by":"crossref","first-page":"e12538","DOI":"10.1371\/journal.pone.0012538","article-title":"Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer\u2019s disease","volume":"5","author":"Astarita","year":"2010","journal-title":"PloS One"},{"key":"10.3233\/JAD-221078_ref14","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.amjmed.2021.06.014","article-title":"The current state of Pharma and the FDA: Approval of a dementia drug as a case in point","volume":"134","author":"Eiser","year":"2021","journal-title":"Am J Med"},{"key":"10.3233\/JAD-221078_ref17","doi-asserted-by":"crossref","first-page":"570711","DOI":"10.3389\/fneur.2020.570711","article-title":"The role of microglia and the Nlrp3 inflammasome in Alzheimer\u2019s disease","volume":"11","author":"Hanslik","year":"2020","journal-title":"Front Neurol"},{"key":"10.3233\/JAD-221078_ref19","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3390\/toxins13100697","article-title":"BMAA, methylmercury, and mechanisms of neurodegeneration in dolphins: A natural model of toxin exposure","volume":"13","author":"Davis","year":"2021","journal-title":"Toxins (Basel)"},{"key":"10.3233\/JAD-221078_ref20","first-page":"20152397","article-title":"Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain","volume":"283","author":"Cox","year":"2016","journal-title":"Proc Biol Sci"},{"key":"10.3233\/JAD-221078_ref23","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/toxsci\/kfab147","article-title":"Neuroinflammatory and neurometabolomic consequences from inhaled wildfire smoke-derived particulate matter in the western United States","volume":"186","author":"Scieszka","year":"2022","journal-title":"Toxicol Sci"},{"key":"10.3233\/JAD-221078_ref24","doi-asserted-by":"crossref","first-page":"e2381","DOI":"10.1212\/WNL.0000000000012973","article-title":"Diet inflammatory index and dementia incidence: A population-based study","volume":"97","author":"Charisis","year":"2021","journal-title":"Neurology"},{"key":"10.3233\/JAD-221078_ref25","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1176\/appi.ajp.2014.14070878","article-title":"Modifiable predictors of dementia in mild cognitive impairment: A systematic review and meta-analysis","volume":"172","author":"Cooper","year":"2015","journal-title":"Am J Psychiatry"},{"key":"10.3233\/JAD-221078_ref26","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.3233\/JAD-215707","article-title":"Precision medicine approach to Alzheimer\u2019s disease: Successful pilot project","volume":"88","author":"Toups","year":"2022","journal-title":"J Alzheimers Dis"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-221078","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:07:09Z","timestamp":1777370829000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-221078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":21,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3233\/jad-221078","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,14]]}}}