Air Pollution and Alzheimer’s Disease Risk Interact With Premature Aging of Neural Stem Cells and Apolipoprotein E Alleles

2021, 2022

Environmental factors in Alzheimer’s disease (AD) are poorly defined. Recent epidemiological studies strongly associate elevated air pollution (AirPoll) with increased risks for accelerated cognitive loss and AD. We hypothesized that AirPoll impairs neuron replacement in adults, which we confirmed in experiments with mice exposed to AirPoll, which impaired proliferation of neural stem cells (NSC). Maintenance of NSC in older ages is hypothesized as critical for resistance to AD-related pathology and cognitive deficits.

This CureAlz project investigates the molecular pathways of NSC impairments by AirPoll and their relation to brain amyloid peptides believed to drive AD. In Year 1 of this project, we showed that AirPoll damage to NSC is attenuated by an anti-amyloid drug developed by CureAlz investigators and with CureAlz support, BPN-15606. Specifically, single cell studies of messenger RNA show that BPN-15606 attenuates AirPoll impairment of neurogenesis in adult brains. These pathways will be analyzed in Year 2 for targets that may protect against AD risk from AirPoll. These studies are the first to examine NSC aging at the single cell level for modulation by AirPoll, and for environmental interactions with amyloid peptides. The findings could extend benefits of BPN-15606 and other anti-amyloid drugs to lowering environmental risks of AD.

Moreover, we showed that amyloid beta peptides, amyloid beta 40 and amyloid beta 42, increase sharply after brain maturation in normal mice. This finding parallels the exponential midlife increase of amyloid beta 40 and amyloid beta 42 in aging humans in a rigorous but neglected study by Fukumoto et al., published in the American Journal of Pathology in 2004. Normal brain aging in mice and humans thus increases amyloid beta peptides, which may predispose humans to AD.


Funding to Date



Studies of APP and Abeta, Translational


Caleb Finch, Ph.D.

Michael A. Bonaguidi, Ph.D.