GR@ACE - Genomic Research at Fundació ACE

Obra Social la Caixa, Grifols, Instituto de Salud Carlos III & Fundación ACE

The GR@ACE project aims to discover new genes that cause Alzheimer's and use this information to propose new treatments to combat the disease.

The GR@ACE project (Genomic Research Applied to Alzheimer's Disease) aims to discover new genes that cause Alzheimer's and use this information to propose new treatments to combat the disease. GR@ACE is part of a priority research line for Europe (Horizon 2020 programme).

In the first phase of the project, a complete scan of the genome has been carried out with the existing samples in Fundació ACE collection which, with more than 10,000 blood collection samples, is the largest in the world collected in a single centre.

The GR@ACE project has identified three categories of genes involved with Alzheimer's disease. The quality and homogeneity of the samples will be key to the design of new strategies and the promotion of combined therapies for the treatment of dementia. In total, the genome of 12,368 people has been analysed during this first phase, 6,063 of whom have Alzheimer's type dementia.

Three gene categories

Fundació ACE carries out an interdisciplinary and exhaustive clinical process in which, in addition to making a diagnosis, a technical classification is also assigned within the diagnosis of Alzheimer's which has to do with the greater or lesser probability that the person may suffer another dementia in addition to Alzheimer's.

Taking into account the diagnosis of Alzheimer's and the probability of suffering another type of dementia simultaneously, groups of patients have been generated for the study, in a pioneering approach in the world of genetic research. This clinical perspective of the analysis is what has made it possible to distinguish the following categories:

  • The first category is that of genes that are stable and their effect remains the same in all groups.
  • Genes in the second category reinforce their effect in groups of patients who have Alzheimer's and who have no other dementia involved..  
  • Genes in the third show more effect in samples from those who, despite having Alzheimer's, are diagnosed as having another dementia.

This distinction of gene behaviour is crucial, firstly, because it points to the possibility of adapting treatment strategies to the type of diagnosis each person has. And secondly, because each of these categories allows scientists to distinguish the area of the genome where these genes act.

Thus, the results of the categorization have shown the relationship of the immune system with all the groups of Alzheimer's samples and the outstanding presence of vascular processes, as causal factors of the disease.


Two new genes

On the other hand, Fundació ACE team has carried out a classic genome tracking study with the same samples, comparing the genetics of all cases, both of people with Alzheimer's and of those who do not suffer from this pathology.

In this study, in addition to the sample from the GR@ACE project, genetic information from other studies has been integrated, reaching a final sample of 81,455 people. This analysis has made it possible to detect two new genes related to Alzheimer's disease.

Although further studies will be necessary to corroborate it, the new genes could be related to the enzyme that synthesizes cholesterol and to the process of neuronal death, respectively.

Data sheet

Start date

22/01/2016


End date

Active


Sponsors / funders

Fundació Obra Social la Caixa, Grifols, Fundació ACE, Instituto de Salud Carlos III


Budget

1.250.000 €


Project leader at Fundació ACE

Dr. Agustín Ruiz, Chief of the Research Unit


Participants

Fundació ACE Research Team and State Consortium DEGESCO


Links of interest:

Scientific publications

P2‐139: Genome-wide association study of Alzheimer’s disease (ad) susceptibility using the Fundacio ACE genome repository: the GR@ACE project 
Alzheimer's Association International Conference; July 23, 2018. doi: https://doi.org/10.1016/j.jalz.2018.06.825.
Sonia Moreno-Grau, Isabel Hernandez, Laura Montrreal, Itziar de Rojas, Montserrat Alegret, Sergi Valero, Adelina Orellana, Lluis Tarraga, Mercè Boada, Agustín Ruiz et al.


Genome‐wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project. 
Alzheimer’s & Dementia 15 (2019) 1333-1347. doi: https://doi.org/10.1016/j.jalz.2019.06.4950.
The GR@ACE study group and DEGESCO consortium.


The MAPT H1 Haplotype Is a Risk Factor for Alzheimer's Disease in APOE ε4 Non-carriers.
Frontiers in Aging Neuroscience, 04 Dec 2019. doi: 10.3389/fnagi.2019.00327.
Sonia Moreno, Itziar de Rojas, Isabel Hernández, Sergi Valero, Montse Alegret, Laura Montrreal, Adelina Orellana, Lluís Tárraga, Mercè Boada and Agustín Ruiz et al. on behalf of GR@ACE Study Group and DEGESCO Consortium.


Common variants in Alzheimer's disease: Novel association of six genetic variants with AD and risk stratification by polygenic risk scores. 
MedRxiv preprint; January 17, 2020. doi: https://doi.org/10.1101/19012021.
Itziar de Rojas, Sonia Moreno-Grau, Mercè Boada, Agustín Ruiz et al.