Apolipoprotein E4, gender, body mass index, inflammation, insulin resistance, and air pollution interactions: Recipe for Alzheimer's disease development in Mexico City Young Females

Lilian Calderón-Garciduẽnas, Suzanne M. de la Monte

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre-and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins. Exposures are associated with early brain gene imbalance in oxidative stress, inflammation, innate and adaptive immune responses, along with epigenetic changes, accumulation of misfolded proteins, cognitive deficits, and brain structural and metabolic changes. The Apolipoprotein E (APOE) 4 allele, the most prevalent genetic risk for AD, plays a key role in the response to air pollution in young girls. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5-2 SD from average IQ). This review focused on the relationships between gender, BMI, systemic and neural inflammation, insulin resistance, hyperleptinemia, dyslipidemia, vascular risk factors, and central nervous system involvement in APOE4 urbanites exposed to PM2.5 and magnetite combustion-derived iron-rich nanoparticles that can reach the brain. APOE4 young female heterozygous carriers constitute a high-risk group for a fatal disease: AD. Multidisciplinary intervention strategies could be critical for prevention or amelioration of cognitive deficits and long-term AD progression in young individuals at high risk.

Original languageEnglish
Title of host publicationAlzheimer's Disease and Air Pollution
Subtitle of host publicationThe Development and Progression of a Fatal Disease from Childhood and the Opportunities for Early Prevention
PublisherIOS Press
Pages437-454
Number of pages18
ISBN (Electronic)9781643681597
ISBN (Print)9781643681580
DOIs
StatePublished - May 3 2021

Keywords

  • APOE
  • Alzheimer's disease
  • Body mass index
  • Children
  • Cognition
  • Dementia
  • Diabetes
  • Female gender
  • Glucose
  • Insulin resistance
  • Leptin
  • Metabolic syndrome
  • Mexico city
  • Nanoparticles
  • PM 2.5

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