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: In the US, African Americans (admixed with African and European) followed by Hispanics (admixed with Amerindian, African, and European) are the most affected groups compared to non-Hispanic Whites (NHW). While genetic diversity and admixture play crucial roles in disease risk, the ancestry-specific mechanisms remain poorly understood with most AD-related studies focusing on NHW. Despite the recent field efforts to include genetically admixed populations, there continues to be a lack of functional studies in AD across the different cell types in these populations.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) are consistently discovering genetic variants linked to the risk of developing this neurodegenerative condition. However, the effect size of the shared associated loci varies across populations as well as each population can have unique associations. This phenomenon could be explained by ancestry-dependent changes in the genomic regulatory architecture (GRA) influencing the expression of these genes, similar to the effect of different local ancestry on the risk of AD in APOE4 carriers.

Basic Science and Pathogenesis.

Amerindian (AI) populations are substantially underrepresented in AD genetic studies. The Alzheimer's Disease Sequencing Project (ADSP), a global genetic initiative established by the National Institute of Aging (NIA) is supporting regional initiatives in Latin America and its admixed population. Latin America is the largest recently admixed population, with variable Native American, European, and African ancestry proportions, as result of successive settlements and new massive migrations.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

Introduction: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care.

Methods: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm.

Results: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted.

Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene.