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

Bibliographic Collection: 
CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Haghani, Amin; Thorwald, Max; Morgan, Todd E; Finch, Caleb E
Year of Publication: 2020
Journal: Alzheimers Dement
Date Published: 2020 Nov 20
Publication Language: eng
ISSN: 1552-5279

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.

DOI: 10.1002/alz.12230
Alternate Journal: Alzheimers Dement