期刊
ALZHEIMERS & DEMENTIA
卷 17, 期 2, 页码 175-190出版社
WILEY
DOI: 10.1002/alz.12230
关键词
aging; air pollution; Alzheimer's disease; apolipoprotein E; chromosome 19q13
资金
- CureAlzheimer's Fund
- National Institutes onAging [R01AG051521, P50-AG005142, P01-AG055367]
Little is known about gene-environment interactions for Alzheimer's disease risk factors. This study reveals novel connections among the APOE network, air pollution, and age-related diseases. Both humans and mice show coordinated responses to air pollution exposure in the cerebral cortex and age-related decline in APOE cluster expression in vulnerable brain regions.
Little is known of gene-environment interactions for Alzheimer's disease (AD) risk factors. Apolipoprotein E (APOE) and neighbors on chromosome 19q13.3 have variants associated with risks of AD, but with unknown mechanism. This study describes novel links among the APOE network, air pollution, and age-related diseases. Mice exposed to air pollution nano-sized particulate matter (nPM) had coordinate responses of Apoe-Apoc1-Tomm40 in the cerebral cortex. In humans, the AD vulnerable hippocampus and amygdala had stronger age decline in APOE cluster expression than the AD-resistant cerebellum and hypothalamus. Using consensus weighted gene co-expression network, we showed that APOE has a conserved co-expressed network in rodent and primate brains. SOX1, which has AD-associated single nucleotide polymorphisms, was among the co-expressed genes in the human hippocampus. Humans and mice shared 87% of potential binding sites for transcription factors in APOE cluster promoter, suggesting similar inducibility and a novel link among environment, APOE cluster, and risk of AD.
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