title: Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models.
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.
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cacciottolo
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Psychology, University of Wisconsin, Milwaukee, WI, USA.
authors.forename: I
authors.initials: I
authors.lastname: Driscoll
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Woodward
authors.affiliation: USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Saffari
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Reyes
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Serre
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: W
authors.initials: W
authors.lastname: Vizuete
authors.affiliation: USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Sioutas
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Morgan
authors.affiliation: Department of Psychology, University of Southern California, Los Angeles, CA, USA.|Memory and Aging Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gatz
authors.affiliation: Memory and Aging Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Neurology, Keck School of Medicine, University of Southern California,, Los Angeles, CA, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Chui
authors.affiliation: Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Shumaker
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Resnick
authors.affiliation: Division of Public Health Services, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Espeland
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.|Memory and Aging Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Finch
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Memory and Aging Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Chen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000453:epidemiology* / Q000235:genetics; D003704:Dementia / Q000453:epidemiology* / Q000235:genetics; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D052638:Particulate Matter; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D052638:Particulate Matter; D018091:Receptors, AMPA