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The APOE gene cluster responds to air pollution factors in mice with coordinated expression of genes that differs by age in humans.
Haghani, Amin; Thorwald, Max; Morgan, Todd E; Finch, Caleb E.
Afiliação
  • Haghani A; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
  • Thorwald M; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • Morgan TE; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
  • Finch CE; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Alzheimers Dement ; 17(2): 175-190, 2021 02.
Article em En | MEDLINE | ID: mdl-33215813
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Expressão Gênica / Poluição do Ar / Apolipoproteína C-I / Doença de Alzheimer Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Expressão Gênica / Poluição do Ar / Apolipoproteína C-I / Doença de Alzheimer Idioma: En Ano de publicação: 2021 Tipo de documento: Article