$12 million NIH grant supports study of Alzheimer’s risk factors
Initiative to explore why Caribbean populations are disproportionately affected, identify new drug targets
Getty ImagesResearchers at WashU Medicine will investigate genetic and molecular factors behind Alzheimer’s prevalence in Caribbean populations. This groundbreaking study, supported by NIH funding, aims to enhance personalized care, diagnostics and treatment strategies for patients worldwide.
Building on its longstanding leadership in Alzheimer’s disease genetics and biomarkers, Washington University School of Medicine in St. Louis has launched the Caribbean Omics & Genomics for Alzheimer Study (CONGAS) with the support of a five-year, $12 million grant from the National Institute on Aging, part of the National Institutes of Health (NIH).
The central mission of CONGAS is to understand why Alzheimer’s disproportionately affects Caribbean and Hispanic populations and identify the genetic and molecular drivers behind this disparity. Ultimately, these insights will bring scientists closer to more precise and personalized diagnostic tools and treatments and help identify new drug targets.
The collaborative project is driven by Carlos Cruchaga, PhD, the Barbara Burton and Reuben M. Morriss III Professor in the Department of Psychiatry; Jorge Llibre-Guerra, MD, an assistant professor in the Department of Neurology; and Laura Ibanez, PhD, an assistant professor in the Department of Psychiatry, all at WashU Medicine. A fourth collaborator, Victoria Fernandez, PhD, began the work while at WashU Medicine and is now head of the genomics unit at ACE Alzheimer Center Barcelona in Spain.
The study will characterize genetic data, blood biomarkers and large-scale proteomics from about 5,000 people in Puerto Rico, Dominican Republic, Costa Rica and Spain. These data will then be integrated with more than 70,000 additional genomes, including more than 10,000 from Hispanic and Latino participants from the Alzheimer’s Disease Sequencing Project (ADSP), an NIH-funded effort to broaden Alzheimer’s research in the U.S. beyond European-ancestry populations. Cruchaga, Llibre-Guerra and their collaborators will analyze this massive dataset to discover new risk factors and modifiers to determine whether genes known to be involved in Alzheimer’s exert different effects in people of Caribbean ancestry.
“Countries in the Caribbean provide the ideal environment to dissect genetic risk,” said Cruchaga, who is also the founding director of the NeuroGenomics and Informatics Center at WashU Medicine. “Because they reflect a long history of genetic mixing among people of African, European and Native American ancestry, the known risk genes for Alzheimer’s disease may behave very differently in this population, or novel risk variants not seen in European cohorts may be driving disease. By studying people with an array of different genetic backgrounds, we can discover new risk factors and protective factors, which we can model for potential new interventions and drugs.”
For example, Cruchaga noted that a genetic variant known as ApoE4 is a risk factor for Alzheimer’s disease, but its effect varies between white and Black populations. An international team co-led by Cruchaga found that another gene, TREM2, influenced Alzheimer’s risk, but not in a uniform way: some variants protected people while others increased their risk. As in ApoE4, the differential effect of TREM2 was observed in individuals with African ancestry. Cruchaga and Llibre-Guerra expect the study of Caribbean individuals to reveal more examples like these.
The new study builds on and complements the ongoing Caribbean Aging and Dementia Study (CADAS) and the GR@ACE cohort at ACE Alzheimer Center. CADAS is an NIH-funded, nationally representative, population-based aging study of adults 65 and older in Puerto Rico and the Dominican Republic that launched in 2021. Researchers recruited participants by going door to door across the islands, an approach to enrollment that removes barriers to participation, such as visiting a clinic, and allows for immediate collection of robust clinical, cognitive, sociodemographic and biological data, including blood samples. The ACE Alzheimer Center is a non-profit institution with over 30 years’ experience in the diagnosis, treatment and study of Alzheimer’s disease and other dementias. It has recruited and banked samples from thousands of individuals, including neurological, neuropsychological and biomarker data.
With the combined dataset from ADSP, CADAS and ACE, Cruchaga, Llibre-Guerra and their collaborators will also investigate how vascular (blood vessel) disease, inflammation and other non-genetic factors contribute to dementia in the Caribbean and Latin America, where “mixed dementia” — a combination of Alzheimer’s and vascular disease affecting the blood vessels of the brain — is more common than it is in the U.S. Those insights could help tailor clinical care for specific populations.
“If we’re able to confirm different genetic effects in this population, that will change how we approach diagnosis, treatment, prevention and the advice we provide to patients,” said Llibre-Guerra, who also serves as the associate director of the Dominantly Inherited Alzheimer Network (DIAN) led by WashU Medicine and has led efforts to add Latin American study sites. “This is an opportunity to illuminate an underexplored area in Alzheimer’s disease and related dementia, which will get us closer to precision medicine and more personalized care and evidence-based decisions for patients based on their risk factors.”
Along with that long-term goal, the researchers expect CONGAS to have near-term impact on Alzheimer’s diagnosis and treatment by refining blood-based biomarker tests that are increasingly used to select patients for clinical trials and therapies. Current tests were largely developed using data from people of European descent, which, Cruchaga said, may lead to a higher number of misdiagnoses.
