Basic Science and Pathogenesis.

Background: Prior studies have shown differences in the genetic etiology and clinical presentation of Alzheimer's Disease across populations. For example, for multiple genetic loci associated with AD, effect sizes can vary drastically between individuals of different ancestral backgrounds. Few investigations into differences in epigenetic features like DNA methylation have been conducted in AD, particularly in diverse individuals.

Basic Science and Pathogenesis.

Background: Polygenic Risk Scores (PRS) are important in predicting disease risk and are usually rely on markers selected by thresholding p-values from genome-wide association studies (GWAS). In traditional approaches, one single model is built to calculate risk scores, employing effect size to determine additive risk. However, this traditional method overlooks potential interactions between genetic loci resulting in reduced prediction power.

Basic Science and Pathogenesis.

Background: Despite its high heritability, the genetic mechanisms influencing Alzheimer's Disease (AD), particularly in health disparity populations like African Americans (AA) and Hispanics (HI), are not fully understood. The lack of ancestral diversity in genetic datasets, notably in eQTL studies that associate genetic variation with gene expression, exacerbates these disparities. Our study seeks to address this gap by comparing the AD interactions of racially and ethnically diverse expression Quantitative Trait Loci (eQTL) effects to investigate the genetic influence on AD in underrepresented populations.

Basic Science and Pathogenesis.

Background: Hispanic/Latino populations are underrepresented in Alzheimer Disease (AD) genetic studies. The Puerto Rican (PR) population, a three-way admixed (European, African, and Amerindian) population is the second-largest Hispanic group in the continental US. We performed a genome-wide association study (GWAS) in the PR population to identify novel AD susceptibility loci and characterize known AD genetic risk loci.

Clinical Manifestations.

Background: The utility of neuropsychological measures commonly used to diagnose individuals with suspected MCI or AD was recently explored in European cohorts, however their utility in Caribbean Hispanic (CH) populations is not well understood.

Method: Our sample consisted of 507 CH individuals from ongoing studies of Puerto Rican and Cuban American older adults (74%% Female, mean age = 74.1, mean education = 12.