Abstract
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer’s disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women’s Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.
Highlights
Environmental influences on Alzheimer’s disease (AD) and related dementias (ADRD) are poorly documented.[1]
Female EFAD transgenic mice (5xFAD+/ − /human Apolipoprotein E (APOE) ε3 or ε4+/+) with 225 h exposure to urban nanosized particulate matter (PM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ε4
There were 173 subjects classified as incident cases of all-cause dementia over an average follow-up of 9.9 years and 329 had global cognitive decline over an average follow-up of 8.3 years
Summary
Environmental influences on Alzheimer’s disease (AD) and related dementias (ADRD) are poorly documented.[1]. Rodent models show long-term neurotoxic effects of air pollutants, including memory impairment[6] and selective atrophy of CA1 hippocampal neurons observed in pre-clinical AD;[7] decreased glutamate receptor subunit GluR1;8 and increased endogenous soluble Aβ.[9,10,11] we lack prospective studies of PM exposure on ADRD risk and interaction with APOE alleles
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
