Native American ancestry and risk of Alzheimer’s disease

Alzheimer’s disease is a neurodegenerative disease that begins as a mild cognitive disorder, but progresses over time to be disabling for those who suffer from it. With some 45 million people affected worldwide, it is the most common form of dementia today. Although factors related to lifestyle (such as diet, sedentary lifestyle or smoking) influence the risk of developing it, between 60 and 80 percent of cases have a genetic basis.

For this reason, scientists seek to identify the genes behind this disease. A difficult task, which is even more complex among the so-called mixed populations, that is, those that do not have a single ancestral origin, but are characterized by the mixture of ethnic groups with diverse genetic background, such as the Argentine population or the Caribbean population. People of Hispanic origin in the Caribbean continue to be underrepresented in medical genetics research. While recent studies have begun to uncover the genetic factors behind Alzheimer’s in Hispanic populations, more is needed to better understand the pathogenesis of the disease in generally mixed populations.

Using innovative statistical methods, an international group led by scientists from the University of Washington (United States) identified genes associated with a lower risk of developing Alzheimer’s disease, the most common form of dementia in the world, in people from the Caribbean of non-Anglo-Saxon origin. And thanks to the genetic basis of the Argentine AGA-ALZAR consortium, in which Laura Morelli, a researcher at the Fundación Instituto Leloir (FIL) and co-author of a new and revealing study published in the academic journal Human Genetics and Genomic Advances, participates, it has been corroborated that this association is due to the prevalence of Native American ancestry, also present in the Argentine population.

Within the framework of the Alzheimer’s Disease Sequencing Project (ADSP) of the United States National Institute on Aging, a group of researchers from the United States, Argentina and Germany identified protective genetic variants on chromosome 13 associated with a reduced risk of developing Alzheimer’s disease. Researchers have determined that this association is linked to “Native American ancestry”, that is, coming from the original settlers of the American continent.

Laura Morelli. (Photo: CyTA-Leloir Agency)

The study, led by researchers from Washington University, in Seattle, United States, focused on the non-Anglo-Saxon population of the Caribbean, with points of contact with that of Latin America and for which “much of the genetic variation that contributes to Alzheimer’s risk is unknown,” Laura Morelli, a CONICET researcher at the Brain Aging and Neurodegeneration Laboratory of the Leloir Institute Foundation (FIL) and co-author of the study, explained to the CyTA-Leloir Agency.

“To corroborate the findings from the Caribbean, the US researchers used genetic data from an independent sample of cases and controls from the Argentine AGA-ALZAR consortium with considerable native ancestry,” said Morelli, who since 2014 has been a member of a team of scientists that participates in the recruitment, processing, analysis and storage of Argentine samples to determine the genetic profile of Alzheimer’s in Argentina. Its ultimate goal is to establish a local risk predictor for the disease.

“These protective variants had not been found before, basically because the statistical analysis was not designed for heterogeneous populations, like ours. By developing a novel method, which ponders the impact of ancestral genes, they found the association”, Morelli stressed. And he clarified: “Now, this data serves to understand and corroborate that genetic diversity is associated with a differential risk of contracting Alzheimer’s. But it still does not have any correlate with clinical practice”.

Morelli, who leads a campaign aimed at obtaining saliva or blood samples from volunteers of Amerindian origin to build a locally representative genetic database, concluded: “In addition to providing concrete data on genes that may favor resilience in Alzheimer’s, the recently published study highlights the importance of having samples of diverse ancestry to improve genetic mapping for this disease.” (Source: CyTA-Leloir Agency)