IN LATIN AMERICA
Colombian individuals with or without various dementias for deleterious variants in disease-causing and risk-con- ferring genes and examined participants’ global and local ancestry proportions. Through these analyses, researchers identified 21 pathogenic variants in Alzheimer’s disease- and fronto- temporal lobar degeneration-motor neuron disease-re- lated genes. PSEN1 harbored the most variants. Unique variants from three continental ancestries — African, European, and Native American — were identified. The results show the significant role that demographic history plays in shaping a population’s genetic risk for disease and emphasize the importance of inclusiveness in genetic studies. THE AGE OF ONSET OF DEMENTIA IS LIKELY LINKED TO GENETIC FACTORS Ongoing studies focusing on the Antioquia family are trying to unravel the mysteries behind the age of onset of dementia. Most individuals in the large Colombian family carrying the PSEN1 E280A mutation develop mild cognitive impairment (MCI) at a median age of 44 and dementia at age 49, although some individuals have been reported to develop MCI nearly three decades after their family’s median age. The predictable age of onset and existence of rare outliers make this family a valuable source of potential genetic variants that delay the onset of Alzheimer’s disease. Dr. Cochran and his lab, along with collaborators at the University of California, Santa Barbara, Universidad de Antioquia, Icahn School of Medicine at Mt. Sinai, and Washington University in St. Louis, were part of a re-
cent study that analyzed the genomes of 344 individuals from the Antioquia family to gain insight into the genetic landscape of age of disease onset 3 . The research team identified several gene candidates that are likely involved in Alzheimer’s disease age of onset, although further studies with more individuals are necessary for confirma- tion. One promising hit was a new variant in the gene CLU , previously implicated as a genetic risk factor for late-onset Alzheimer’s disease. While the Antioquia family is the largest known dominant Alzheimer’s disease family, they still represent a small group for statistical purposes. Recruitment of more patients with early-onset dementias from South American countries will help overcome this limitation in future studies. One such effort to increase Latin American representation in genetic research is Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat) 4 . The multinational effort, which in- cludes Dr. Cochran and his lab, seeks to expand dementia research in Latin America, focusing especially on under- served and diverse populations. The consortium aims to identify the unique genet- ic and socioeconomic determinants of health that drive Alzheimer’s disease and other dementias in Latin Amer- ica. The five-year project aims to collect neuroimaging, genetic and behavioral data on over 4,000 individuals from Argentina, Brazil, Chile, Columbia, Mexico, Peru, and the U.S. to offer a unique understanding of the genetic and environmental underpinnings of dementia. ■
Above, Dr. Cochran explains the population health study results from Antioquia, Columbia.
RESEARCH REPORT
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