Page 81 - Memora anual Fundación CIEN 2017

3. SCIENTIFIC ACTIVITY

Distribution of APOE ε2/ε4 tion of the national consortium in international pro-
genotypes in the CAFRS 4 posals (see below).
patients cohort 1%
In addition to the study of the APOE gene, using
APOE genotypes samples from the Vallecas Project (controls) and
samples from the Alzheimer Project (AD cases), ge-
ε2/ε3 netic association studies of the main genes associa-
ε2/ε2 13 ted with AD have been carried out, including SORL1,
LDLR, BIN1, CLU, ABCA7, CR1, PICALM, BACE1 and
0 3% PRNP. These association studies, in addition to ser-
ε4/ε4 0% ving as a replication in a Spanish population of stu-
dies carried out in other populations, will allow us to
31 determine the most important genetic factors in the
8% development of cognitive dysfunction in our popu-
lation of the Vallecas Project. It will also allow defi-
ε3/ε4 ε3/ε3 ning endophenotypes based on genetic variations
154 187 as well as concrete and measurable characteristics
40% 48% of the patients and controls based on clinical neu-
roimaging, biochemical or pathological measure-
ments (see figure).

in order to identify molecular, clinical, or neuroima- An European DNA bank for deciphering the missing
ging signals that may serve to define populations at heritability of Alzheimer’s disease - EADB (European
higher risk of developing dementia in the future.
AD DNA Bank) and GR@ACE project (Genomic
Dementia Genetics Spanish Consortium Research at Fundació ACE)
(DEGESCO)
This project is an international collaboration initiative
Also, during this year, the CIEN Foundation has con- carried out through DEGESCO that aims at signifi-
tinued participating in Dementia Genetics Spanish cantly increasing the generation of data based on
Consortium (DEGESCO). A number of Spanish rese- GWAS (Genome-Wide Association Studies), through
arch groups share genetic data within this consor- the creation of a European DNA biobank of Alzhei-
tium to achieve greater study power in dementia mer's disease (EADB). In this study, over 30,000 AD
genetics and especially in the Alzheimer's disease. cases and 40,000 controls in 11 countries will be
Because of these collaborations, an interesting study analyzed. GWAS and complementary statistical
on the association of the H1 haplotype of the MAPT analyses will be carried out (based on genotype
gene in non-carriers of the APOE 4 allele has been and imputation data) in order to identify the missing
published. In the context of DEGESCO, during 2016 heritability and pathophysiological mechanisms of
several research actions were carried out aimed at the disease.
defining new genetic risk factors and the participa-
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

CIEN Foundation Annual Report 2017 / 81