# Mechanism of Gene Environment Interactions in Alzheimer's Disease

> **NIH NIH R01** · FLORIDA INTERNATIONAL UNIVERSITY · 2020 · $456,267

## Abstract

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 Aβ
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.

## Key facts

- **NIH application ID:** 9978067
- **Project number:** 5R01ES026057-06
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** Jason R Richardson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,267
- **Award type:** 5
- **Project period:** 2018-10-27 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978067

## Citation

> US National Institutes of Health, RePORTER application 9978067, Mechanism of Gene Environment Interactions in Alzheimer's Disease (5R01ES026057-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978067. Licensed CC0.

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