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ADAM10 levels and activity in different APOE genotypes in healthy elderly people

Grant number: 20/06128-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2020
Effective date (End): June 30, 2021
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Márcia Regina Cominetti
Grantee:Sabrina Cristina da Silva
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Dementia caused by Alzheimer's disease (AD) is the most prevalent dementias in Brazil and in the world and several studies have associated the allele µ4 of the Apolipoprotein E (APOE) as the main genetic risk factor for AD at onset late. The evidence of its negative impact on cognitive functions has been demonstrated in different populations, which include healthy individuals from different ages and seniors with AD. In addition to research on this genetic marker, since 2010, our laboratory has been focusing on investigating the role of ADAM10 protein in the development of the disease. ADAM10 acts as ±-secretase involved in cleavage and inhibits peptide formation ²-amyloid (A²) and ultimately the development of the DA. Our group demonstrated that lower levels of ADAM10 platelets in elderly people with AD, compared to cognitively healthy elderly people. In addition, other groups have shown that ADAM10 levels increase over the cognitively healthy aging. Although the APOE4 genotype is the main genetic risk factor for AD and ADAM10 as a biomarker protein of the disease, there is a lack of studies investigating possible relationship between these two markers. The objectives of this work are to compare the levels and activity of ADAM10 platelet and plasma in the different genotypes of APOE in healthy elderly and check possible relationships between ADAM10 and cognitive functions. This is transversal, observational, comparative study using a quantitative approach. The sample will consist of healthy elderly, stratified according to the APOE genotype. The data collection tools will be: Mini-Mental State Examination, Clinical Assessment Score of Dementia, Geriatric Depression Scale (GDS30). In addition, blood collection will be performed for the determinate the genotype of APOE and quantify ADAM levels and activity10. All ethical precepts that governing research with human beings will be observed. It is hoped that the study can contribute to comprehension of the impact of this genetic marker on healthy elderly.