期刊
TRANSLATIONAL PSYCHIATRY
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tp.2016.280
关键词
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类别
资金
- National Heart, Lung, and Blood Institute (NIH) [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
- Wyeth Pharmaceuticals, St Davids, PA, USA
- Wake Forest University
- NIH [R01AG033078, R01AG051521, R21AG040753, R21AG040683, R00AG032361]
- Cure Alzheimer's Fund
- Southern California Environmental Health Sciences Center [5P30ES007048]
- [RF1AG054068]
- [R21AG0500201]
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 epsilon 4/4 carriers. Female EFAD transgenic mice (5xFAD(+/-)/human APOE epsilon 3 or epsilon 4(+)/(+)) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral beta-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for A beta deposits, both exacerbated by APOE epsilon 4. Moreover, nPM exposure increased A beta 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 epsilon 4 carriers. The underlying mechanisms may involve increased cerebral Aa production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.
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