Using well-characterized clinical cohorts, we recently reported that serum levels of DDE, the metabolite of the organochlorine pesticide DDT is significantly higher in the serum of Alzheimer Disease (AD) cases and is associated with increased risk of AD diagnosis. Further, individuals harboring a polymorphism in APOE and having high serum levels of DDE performed worse on a cognitive task than either those with just the polymorphism or high DDE levels. Finally, we identified that DDT and DDE increase levels of amyloid precursor protein (APP), suggesting a possible mechanism by which DDT exposure may contribute to ADBased on our initial findings, the goals of this project include: (1) identifying the mechanism by which DDT exposure increases APP levels; (2) determining the effect of APOE genetic status on the effects of DDT on A? accumulation and oligomerization; and (3) assessing the effects of DDT exposure on AD pathology and behavioral dysfunction in transgenic mouse models humanized for APOE polymorphisms. We will achieve these goals using a combination of cutting edge techniques including epigenetic analysis, patient-specific stem cells, and transgenic mice harboring human polymorphisms.

Public Health Relevance

This project will provide a comprehensive analysis of the mechanism by which elevated serum DDE levels are associated with AD diagnosis, cognitive function and AD pathology. Further, valuable information on the role of APOE genotype in this relationship will be determined. In turn, this may aid in identifying potential susceptible populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
7R01ES026057-04
Application #
9813822
Study Section
Systemic Injury by Environmental Exposure (SIEE)
Program Officer
Hollander, Jonathan
Project Start
2018-10-27
Project End
2021-06-30
Budget Start
2018-10-27
Budget End
2019-06-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Florida International University
Department
Social Sciences
Type
Schools of Social Welfare/Work
DUNS #
071298814
City
Miami
State
FL
Country
United States
Zip Code
33199
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