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2023 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Functional Analysis of the PSEN1 G206A Variant in Hispanics with Alzheimer's Disease

How does a genetic variation in some Puerto Rican families lead to early-onset Alzheimer’s?

Katrina Celis, M.D.
Miller School of Medicine of the University of Miami
Miami, FL - United States


According to the 2023 Alzheimer’s Association Facts and Figures Report, studies indicate that older Hispanic/Latino American adults are about one and one-half times as likely to have Alzheimer’s or other dementias as older White Americans. The Report also notes that the larger Hispanic American community is a very diverse group of individuals with different cultural histories and health profiles.

Individuals with specific variations in the gene presenilin-1 (PSEN1) develop an early-onset form of Alzheimer’s (i.e., experiencing cognitive symptoms beginning in middle age). Studies show that there may be over 200 genetic variations in PSEN1 that may be associated with the development of Alzheimer’s. Studies also suggest that the different PSEN1 genetic variations may be associated with variability in individual brain changes, age of symptom onset such as memory loss and cognitive decline.

Researchers have found a genetic variation in the PSEN1 gene called G206A in Caribbean Hispanic individuals primarily from Puerto Rico. As part of the Puerto Rico Alzheimer Disease Initiative (PRADI), Dr. Katrina Celis and colleagues have identified 43 carriers of the G206A variation from 18 families. While the majority of PSEN1 variations have an age of onset between 35 and 45 years, the age of onset of G206A carriers in this dataset varies substantially (from 43-86 years). The biological mechanisms driving this variability are unknown.

Research Plan

Dr. Celis and colleagues will study the impacts of the G206A variation using brain samples and a special type of stem cell from G206A carriers identified in the PRADI cohort called induced pluripotent stem cells (iPSCs). iPSCs are collected from adult tissue and can be programmed to grow into any type of cell in the body, including nerve cells. 

The researchers will perform RNA sequencing on the brain tissue and iPSCs derived from G206A carriers with different ages of onset of Alzheimer’s. They will also grow iPSCs into three-dimensional cultures of nerve cells and other types of brain cells and characterize how they function in a laboratory dish.


The findings may improve our understanding of how genetics influences the progression of Alzheimer’s and may also help identify potential novel therapies that could benefit individuals with specific Alzheimer’s-related genetic variations.

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