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tion studies of the main genes associated with AD have been carried out, including SORL1, LDLR, BIN1, CLU, ABCA7, CR1, PICALM, BACE1 and PRNP. These association studies, in addition to serving as a replication in a Spanish population of studies carried out in other populations, will allow us to determine the most important genetic factors in the development of cognitive dysfunction in our population of the Vallecas Project. It will also allow defining endophenotypes based on genetic variations as well as concrete and measurable characteristics of the patients and controls based on clinical neuroimaging, biochemical or pathological measure- ments (see figure).
Illustration of the concept of endophenotypes for defining homogenous popu- lations based on certain genetic variants and biomarkers in Alzheimer’s disease (modified from During et al. 2011)
• A European DNA bank for deciphering the missing heritability of Alzheimer’s dis- ease - EADB (European AD DNA Bank) and GR@ACE project (Genomic Research at Fundació ACE)
This project is an international collaboration initiative carried out through DEGES- CO that aims at significantly increasing the generation of data based on GWAS (Genome-Wide Association Studies), through the creation of a European DNA bio- bank of Alzheimer’s disease (EADB). In this study, over 30,000 AD cases and 40,000 controls in 11 countries will be analyzed. GWAS and complementary statistical analyses will be carried out (based on genotype and imputation data) in order to identify the missing heritability and pathophysiological mechanisms of the dis- ease.
This initiative will increase the number of AD samples available in Europe more than four times and around the world by almost two-fold. Carrying out this pro- ject will allow us to understand the genetics of AD thus improving our knowledge of the underlying pathophysiological processes in the disease; since the genetic factors seem to represent up to 80% of the attributable risk in AD. In parallel, the EADB will collect DNA samples from the largest European longitudinal cohort of cases of mild cognitive impairment, with the aim of identifying genetic mark- ers that modulate the rate of disease progression and cognitive decline. From a translational perspective, the identification of genetic factors in the pathways that modulate AD risk and increase the rate of disease progression/cognitive de- cline will be critical for the development and testing of therapeutic approaches. Additionally, in the context of the DEGESCO consortium, collaboration has begun with the GR@ACE project, led by the ACE Foundation, which will be carried out in three years, and whose objective is the application of high resolution genomic technologies for the identification of a new generation of genes that contribute data in the design of new treatments to deal with Alzheimer’s disease.
In relation to the study of biomarkers and the collaborative context with the com- pany Biocross SL and with various Spanish hospitals, we continue with the plasma metabolomic studies of people with Alzheimer’s disease, mild cognitive impair- ment or without cognitive dysfunction. In addition, we also continue with the de-
3. Scientific activity
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