Affiliations: [a] Penn Center for Public Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| [b] Environmental Neuroscience Group, Center for Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA, USA
| [c] Center on Aging, University of Sherbrooke, Quebec, Canada
Correspondence:
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Correspondence to: Arnold R. Eiser, MD, MACP, 1316 Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Tel.: +1 610 209 8106; E-mail: arnold.eiser@pennmedicine.upenn.edu.
Abstract: 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’s 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.
