The APOE gene cluster responds to air pollution factors in mice with coordinated expression of genes that differs by age in humans.

Alzheimer's & Dementia : the Journal of the Alzheimer's Association
Amin HaghaniC E Finch

Abstract

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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Citations

Dec 20, 2020·Mechanisms of Ageing and Development·Svetlana UkraintsevaAnatoliy Yashin
Feb 14, 2021·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Caleb E Finch, Amin Haghani

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