2025 American Academy of Neurology Abstract Website

Objective:

Using the All of Us data, our study will evaluate the association of ACE gene
polymorphisms with AD risk in the Hispanic population.

Background:

Alzheimer's disease (AD) is a neurodegenerative disorder mainly affecting individuals 65 and older, marked by cognitive decline and amyloid-beta (Aβ) plaque accumulation. Hispanics have a 12.2% prevalence of AD, making them the second-highest ethnic group in the U.S., with the largest projected increase. While environmental and genetic factors contribute, the precise pathophysiology remains unclear. The ACE (Angiotensin Converting Enzyme) gene, involved in Aβ degradation, has been linked to AD. Various ACE gene polymorphisms (rs4291, rs4309, rs4343, rs4351) have been studied, but not in the Hispanic population. We hypothesized that ACE gene polymorphisms in Hispanics will be associated with AD and can be used as an AD risk factor to assess clinically.

Design/Methods:

This study included 73,491 Hispanic participants from the All of Us data. ACE genotypes (rs4291, rs4309, rs4343, and rs4351) were assessed for AD risk in the Hispanic population. Fischer's exact test and multinomial logistic regression were applied to predict the association between ACE gene polymorphisms and AD.

Results:

The ACE gene polymorphisms in the Hispanic population showed frequencies of 57.22% for rs4291, 45.85% for rs4309, 52.49% for rs4343, and 49.58% for rs4351. Rs4343 (OR = 1.481, p < .05) and rs4351 (OR = 1.461, p < .05) were significantly associated with an increased risk of Alzheimer's disease. However, no significant associations were found between rs4291 and rs4309 and AD risk.

Conclusions:

The association of ACE gene polymorphisms rs4343 and rs4351 with Alzheimer's disease in the Hispanic population is a noteworthy finding. Screening for these variants could help identify individuals at higher risk, enabling early detection and targeted interventions to potentially mitigate disease progression.