Looking for a genetic molecular signature for Alzheimer?s Disease in Argentina

MUCHNIK, C; OLIVAR, N; DALMASSO, MC; KELMANSKY, D; MORELLI, L; ACION, L; BRUSCO, LI

C.A.B.A.

Congreso; 2nd FALAN CONGRESS; 2016

Federation of Latin American and Caribbean Neuroscience Societies (FALAN)

The identification of Single Nucleotide Polymorphism (SNPs) as susceptibility genetic factors for Late Onset Alzheimer?s Disease (LOAD) remarkably contributes to better understand pathophysiology of the disease, to improve its prognosis, and to set the populationat risk. Genetic risk factors may differ within ethnicity of populations. Thus, our main goal is to obtain a genetic molecular signature for LOAD in the Argentine population, in order to build a LOAD-risk genetic panel that, in combination with other clinicalrisk factors, would help to estimate the chances of developing the disease. To this aim we will employ two strategies: 1) looking for significant SNPs among the ones already described in Caucasian population, and 2) discovering new relevant SNPs in our populationby Genome-Wide Association Studies (GWAS). To date, we have performed a case-control study with subjects from Buenos Aires that were genotyped for 95 SNPs previously associated to LOAD, and 97 SNPs to evaluate ancestry. We obtained a group of 23 SNPs statisticallysignificant by several tests. Except for the validated APOE4, these 23 SNPs differ from the top SNPs identified in Caucasian population by GWAS. In addition, we studied several TREM2 gene variants to validate them as risk factors in our population. Finally,we are using Targeted-Learning method (a machine-learning algorithm and statistics combiantion) to test all these results and evaluate its potential to develop a LOAD predictive algorithm.