Quantification of encephalic transcripts of the APOE allele specific gene of European and African ancestry

• Published in: Alzheimer's & dementia Vol. 19; no. S12
• Main Authors: Nascimento Santos, Gabriel, Suemoto, Claudia Kimie, Ferretti‐Rebustini, Renata Eloah de Lucena, Rodriguez, Roberta Diehl, Grinberg, Lea T., Pasqualucci, Carlos Augusto, Brito, Luciano Abreu, Scliar, Marília Oliveira, Leite, Renata Elaine Paraizo, Araujo, Nathalia Matta, Borda, Victor, Tarazona‐Santos, Eduardo, Jacob‐Filho, Wilson, Nitrini, Ricardo, Yaffe, Kristine, Zatz, Mayana, Haddad, Luciana Amaral, Naslavsky, Michel S
• Format: Journal Article
• Language: English
• Published: 01-12-2023
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.076340

Background
The APOE gene is identified as a major risk factor for late onset Alzheimer’s disease and has three alleles, ε2, ε3 and ε4, related to two non‐synonymous substitutions. The presence of the ε4 allele confers an increased risk for the disease in a dose dependent manner (odds ratio 12.9 for homozygous individuals and between 3.2 and 4.2 for heterozygous individuals). The most prevalent form of Alzheimer’s disease has a multifactorial etiology, where several genetic and environmental factors influence its pathology. Factors such as age and sex are relevant in determining the risk for APOE, recent studies point out that the ancestry around the APOE gene is also relevant to the risk for the disease. Individuals of African‐American ancestry have a reduced risk of developing the disease compared to European and Asian whites. These regions may act in a cis‐regulatory manner in modulating gene expression. The Brazilian population results from miscegenation between indigenous, African and European populations, offering an opportunity to study the effects of different ancestries on the risk of Alzheimer’s disease, fill the lack of genetic information about admixed groups and characterize the differential patterns of APOE’s expression in Brazilian population.
Method
This project aims to quantitatively characterize the role of different local ancestry in the different APOE genotypes using 36 post‐mortem brain tissue, with distinct genotypes and local ancestries combinations (33,34,44, European‐European, African‐African, European‐African, African‐European) and associating them with the expression of this gene through molecular marker genotyping and RT‐qPCR techniques. It is expected that the mRNA expression is differentially increased when European local ancestry is shown to be present, compared to non‐European ancestry and may explain, in part, the difference in risks observed in populations of different ancestries.
Result
ongoing research
Conclusion
ongoing research