# Cardiovascular Genotype and APOE ε4 Carrier Status Interaction Effects on Amyloid Load in Pre-Clinical Alzheimer's Disease

> **NIH NIH R03** · BANNER HEALTH · 2023 · $89,078

## Abstract

Project Summary
 Research and treatment approaches in pre-clinical Alzheimer's disease (AD) have focused primarily on the
deposition and clearance of beta-amyloid which leads to the formation of cortical plaques and neurofibrillary
tangles, a hallmark of AD pathology. However, the role that vascular factors may have in the development of
these pathologies is not clear. Epidemiological studies have suggested that risk factors such as high cholesterol,
hypertension, type 2 diabetes, and inflammation are associated with an increased risk of developing AD. Several
studies have demonstrated that certain cardiovascular genetic markers are associated with clinical AD and its
pathological hallmarks. Specific polymorphisms of the CRP gene (rs3091244, and rs3093075) are associated
with greater plaque load while the rs1205 and rs2794521 polymorphisms appears to protect against amyloid
deposition. The methylenetetrahydrofolate reductase (MTHFR) gene has been implicated as a susceptibility
marker for AD and is also recognized as an important factor in cardiovascular disease due to its role in regulating
homocysteine. The MTHFR C677T (rs1801133) polymorphism is a marker of interest in both the AD and
cardiovascular contexts and it is noted that this polymorphism interacts with APOE carrier status on
cardiovascular outcomes. There is also evidence that the rs1801131 polymorphism influences the risk of AD and
has shown to moderate the effect of APOE on AD risk. Vascular endothelial growth factor (VEGF) has also been
implicated in AD as the C2578A allele (rs699947) has been associated with an increased risk for AD in which a
significant VEGF by APOE interaction may play a role. The G1154A (rs1570360) polymorphism of VEGF has
shown to have a protective effect for AD. The kinesin family member 6 (KIF6) gene's 719Arg polymorphism
(rs20455) has been strongly implicated in the risk for cardiovascular events, but its possible role in AD has not
been fully investigated. The rs3025039 polymorphism has also shown consistent associations with
cardiovascular disease however its link with AD risk or pathology is unknown. The aim of this study will be to
examine the effects of these cardiovascular gene markers on imaging-based measures of amyloid in cognitively
unimpaired older adults. This study will also explore whether the interactions between APOE e4 carrier status
and these alleles are associated with in vivo plaque and tangle load.

## Key facts

- **NIH application ID:** 10664432
- **Project number:** 1R03AG077270-01A1
- **Recipient organization:** BANNER HEALTH
- **Principal Investigator:** Michael Malek-Ahmadi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $89,078
- **Award type:** 1
- **Project period:** 2023-06-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10664432

## Citation

> US National Institutes of Health, RePORTER application 10664432, Cardiovascular Genotype and APOE ε4 Carrier Status Interaction Effects on Amyloid Load in Pre-Clinical Alzheimer's Disease (1R03AG077270-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10664432. Licensed CC0.

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