2023 Alzheimer's Association Clinical Scientist Fellowship to Promote Diversity (AACSF-D)
Sex, socioeconomical and genetic risk factors in early AD-type pathology
Does a higher prevalence of Alzheimer's in females in Brazil provide insights into the underlying biological mechanisms?
Karen Luiza Ramos Socher, M.D.
University of Sao Paulo
São Paulo, Brazil
Background
A complicated mix of genetic, environmental, sex, and lifestyle factors influence the development of Alzheimer’s. Developing countries like Brazil may hold some clues on how to disentangle these multiple influences: among the growing number of individuals diagnosed with Alzheimer’s, over 60% are women. This bias suggests there are sex-specific factors that may increase risk, either through female biology or through their life experiences. In addition, the mixed genetic ancestry of Latin American populations provides an opportunity to look for novel genetic factors related to Alzheimer’s, and to test whether well-known risk factors like the APOE e4 gene variant acts similarly in these populations.
Research Plan
Dr. Socher plans to use a unique Brazilian biobank, which has brain donations from individuals who have been comprehensively evaluated, including information on their clinical signs of dementia, medical history, and lifestyle-related factors such as socioeconomic status. There are also DNA samples are available through this biobank for genetic characterization. Dr. Socher plans to study the brain samples to look for signs of Alzheimer’s, and to see how they relate to individual characteristics, such as sex, genetics, and socioeconomic status.
Previous studies suggest more tau tangles (another hallmark brain change in Alzheimer’s) in the brain of females than in males with Alzheimer’s. However, this finding has only been confirmed in some populations. The reseacherers will image brain tissue from the Brazilian biobank to study the levels of tau tangles in the brains of this population. Once the tau tangles have been counted , Dr. Socher will conduct an analyses to see if there are more tau tangles in females than in males in this population. Other variables will also be incorporated into the data analyses to see how various factors influence NFT burden; these additional factors will include APOE genotype, genetic ancestry, socioeconomic status, medical history, and clinical symptoms of dementia-related difficulties.
Impact
This study in a poorly-researched Brazilian population has the potential to identify important risk factors for Alzheimer’s. These factors may offer novel strategies to lower dementia prevalence in developing countries and beyond.