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.

Review of recent researches on air pollution effects on human cognitive functions

“…In addition, results of this study showed a strong relationship between traffic-related air pollution and child's attention within long-term contact with air pollution compared to short-term contact [4]. Another study was conducted by M Cacciottolo and his colleagues under the title of "particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models" [5]. Authors of this research have expressed that exposure to air particulates (PM) and its interaction with APOE alleles may contribute to aging brain and Pathogenesis of Alzheimer's Disease (AD).…”

“…Results obtained from this study showed that living in places consisting of PM levels higher than EPA standards increases the risk of cognitive disorder and dementia equal to 81% and 92%, respectively so that such pollution has destructive effects on AP-OE 4.4 carriers. Infrastructural mechanisms may include increased brain Aβ production and changed CA1 hippocampal neurons and glutamate receptor subunits [5]. Another study was conducted by Jeanette A.Stingone and colleagues under the title of "using machine learning to identify air pollution exposure profiles associated with early cognitive skills among U.S. children"; this study was conducted in medical department of social health and environment in Sinai School of Medicine in New york [6].…”

“…Infrastructural mechanisms may include increased brain Aβ production and changed CA1 hippocampal neurons and glutamate receptor subunits [5]. Another study was conducted by Jeanette A.Stingone and colleagues under the title of "using machine learning to identify air pollution exposure profiles associated with early cognitive skills among U.S. children"; this study was conducted in medical department of social health and environment in Sinai School of Medicine in New york [6]. Machine learning methods using data create an opportunity for simultaneous evaluation of effect of several air pollutants on health.…”

“…Instruments of this test consisted of initial mathematical abilities. Children who live in regions with higher Isophorone had lower math scores, while exposure to Trichloroethylene indicated no relation with math scores [6]. Jennifer Ailshire and colleagues conducted a study entitled "neighborhood social stressors, fine particulate matter air pollution, and cognitive function among older U.S. adults" in USC Leonard Davis School of Gerontology, University of Southern California, Los Angeles to investigate the cognitive function and effect of air pollution [7].…”

Introductory lecture: atmospheric chemistry in the Anthropocene

“…A mechanistic basis for the effects of PM may be translocation of particles to the brain. 75,[84][85][86] Interestingly, cognitive decits due to air pollution were suggested around the year 1200, when the philosopher Maimonides attributed "dullness of understanding, failure of intelligence and defect of memory" to air pollution.…”