Particulate matter and Alzheimer’s disease: an intimate connection

Worldwide, individuals are routinely exposed to levels of particulate matter (PM) above the air quality guideline levels set by the World Health Organization (WHO), placing them at risk for developing PM-induced diseases. PM enters the body and affects the progression of numerous diseases, many of which impact vital organs such as the heart, lungs, brain, and gut. PM may infiltrate the brain and engender the development of numerous cognitive diseases by crossing the blood–brain barrier or traveling through the olfactory bulb. PM exposure and Alzheimer’s disease (AD) development are strongly correlated and PM is believed to exacerbate AD development via a complex interplay of mechanisms. Treatments for AD remain limited, but a deeper understanding of the risk factors and AD pathogenesis will enable researchers to design studies aimed to mitigate AD symptoms and development. The environmental role in disease progression has been appreciated for decades; however, understanding how airborne toxicant exposure can affect organs beyond the lungs is an underappreciated area of scientific inquiry. Particulate matter (PM) includes various gases, liquids, and particles in suspension and is produced by industrial activities such as fossil fuel combustion and natural events including wildfires and volcanic eruptions. Although agencies have attempted to reduce acceptable airborne particulate levels, with urbanization and population growth, these policies have been only moderately effective in mitigating disease progression. A growing area of research is focused on the role of PM exposure in the progression of Alzheimer’s disease (AD). This review will summarize the knowns and unknowns of this expanding field. The environmental role in disease progression has been appreciated for decades; however, understanding how airborne toxicant exposure can affect organs beyond the lungs is an underappreciated area of scientific inquiry. Particulate matter (PM) includes various gases, liquids, and particles in suspension and is produced by industrial activities such as fossil fuel combustion and natural events including wildfires and volcanic eruptions. Although agencies have attempted to reduce acceptable airborne particulate levels, with urbanization and population growth, these policies have been only moderately effective in mitigating disease progression. A growing area of research is focused on the role of PM exposure in the progression of Alzheimer’s disease (AD). This review will summarize the knowns and unknowns of this expanding field. 40-residue peptide derived from the cleavage of the protein amyloid precursor protein; it is a major component of Aβ plaques. 42-residue peptide derived from the cleavage of the protein amyloid precursor protein; it is a major component of Aβ plaques. insoluble extracellular aggregations produced from the processing of amyloid precursor protein (APP) by β- and γ-secretases. a functional imaging technique that detects the presence of amyloid in brain tissue and brain blood vessels by detecting positrons emitted during the decay of a radioisotope-labeled ligand that binds to amyloid. derived from human activity, not naturally occurring. a multifunctional protein that is mainly involved in the transportation of lipids through the cerebrospinal fluid and plasma while simultaneously being a risk factor for AD pathology. The APOE-ε4 allele is the most risk-inducing allele for the development of AD. the specialized microvasculature that surrounds the brain. The microvasculature consists of nonfenestrated blood vessels with specialized endothelial cells, which tightly regulate what can and cannot pass from the circulating blood system to the brain. an inbred mouse strain widely used in research as a control. outer brain layer responsible for higher level processes, including emotion, thought, language, memory, reasoning, and consciousness. located within the medial temporal lobe and responsible for shuttling information to and from the hippocampus, this structure plays a critical role in memory and navigation. brain structure found within the temporal lobe with major learning and memory responsibilities. an abnormal, pathological form of tau protein found to aggregate and contribute to neurofibrillary tangles and the associated physiological degradation and neuronal death seen in AD patients. cognitive and/or memory decline that is above normal aging, but below diagnostic standards for dementia. Affected persons are able to lead independent lives. The condition may return to normal, remain stable, or progress to dementia. involving the death or dysfunction of cells in the central nervous system. dense intracellular accumulations of the hyperphosphorylated protein tau that contribute to neuronal death. the route by which inhaled particles are translocated from the nasal cavity to olfactory bulb. a transgenic AD rat model that has two mutant alleles associated with AD: APPSwe and PSEN1dE9. a transgenic AD mouse model that has five mutant alleles associated with AD: APPSwe, APPI716V, APPV717I, PSEN1M146L, and PSEN1L286V. a transgenic AD mouse model that has three mutant alleles associated with AD: APPSwe, tauP301L, and PS1M146V.