Air Pollution as an Environmental Risk Factor for Alzheimer's Disease and Related Dementias.

Alzheimer's disease and related dementias are a leading cause of morbidity in our aging populations. Although influenced by genetic factors, fewer than 5% of Alzheimer's disease and related dementia cases are due solely to genetic causes. There is growing scientific consensus that these dementias arise from complex gene by environment interactions. The 2020 Lancet Commission on dementia prevention, intervention, and care identified 12 modifiable risk factors of dementia, including lifestyle, educational background, comorbidities, and environmental exposures to environmental contaminants. In this review, we summarize the current understanding and data gaps regarding the role(s) of environmental pollutants in the etiology of Alzheimer's disease and related dementias with a focus on air pollution. In addition to summarizing findings from epidemiological and experimental animal studies that link airborne exposures to environmental contaminants to increased risk and/or severity of Alzheimer's disease and related dementias, we discuss currently hypothesized mechanism(s) underlying these associations, including peripheral inflammation, neuroinflammation and epigenetic changes. Key data gaps in this rapidly expanding investigative field and approaches for addressing these gaps are also addressed.