GR@ACE – Genomic Research at ACE
Obra Social la Caixa, Grifols, Instituto de Salud Carlos III & Fundació ACE. El projecte GR@ACE és un estudi de genètica humana que té per objectiu descobrir nous gens que provoquen l’Alzheimer i usar aquesta informació per proposar nous tractaments per combatre la malaltia.
The GR@ACE project (Genomic Research Applied to Alzheimer’s Disease) aims to identify new genes that cause Alzheimer’s disease and to use this information to propose new treatments to combat the condition. GR@ACE is part of a research line considered a priority for Europe under the Horizon 2020 programme.
In the first phase of the project, a comprehensive genome-wide scan was carried out using samples from the Ace Alzheimer Center Barcelona collection, which, with more than 10,000 blood samples, represents the largest collection worldwide gathered at a single centre. The GR@ACE project has enabled the identification of three categories of genes involved in 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, during this first phase, the genomes of 12,368 individuals were analysed, 6,063 of whom had Alzheimer-type dementia.
Three gene categories
Ace Alzheimer Center Barcelona conducts a comprehensive interdisciplinary clinical process in which, in addition to establishing a diagnosis, a technical classification within the Alzheimer’s diagnosis is assigned, reflecting the greater or lesser probability that an individual may suffer from another form of dementia in addition to Alzheimer’s disease. Taking into account both the Alzheimer’s diagnosis and the likelihood of developing another type of dementia simultaneously, patient groups were created for the study, using a pioneering approach in the field of genetic research.
This clinically driven analytical perspective made it possible to distinguish the following categories:
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The first category includes genes that are stable, with effects that remain consistent across all groups.
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Genes in the second category show a stronger effect in patient groups with Alzheimer’s disease and no additional dementia.
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Genes in the third category show a greater effect in samples from individuals who, despite having Alzheimer’s disease, present a diagnosis indicating the possible presence of another form of dementia.
This distinction in gene behaviour is crucial, firstly, because it points to the possibility of tailoring treatment strategies to each individual’s diagnostic profile. Secondly, each category allows scientists to identify the genomic regions in which these genes act. Accordingly, the categorisation results have highlighted the involvement of the immune system across all Alzheimer’s sample groups and the prominent presence of vascular processes as causal factors in the disease.
Two new genes
In parallel, the Ace Alzheimer Center Barcelona team carried out a classical genome-wide association study using the same samples, comparing the genetics of individuals with Alzheimer’s disease and those without the condition. In addition to the GR@ACE project samples, genetic information from other studies was integrated, resulting in a final cohort of 81,455 individuals.
This analysis led to the identification of two new genes associated with Alzheimer’s disease. Although further studies will be required to confirm these findings, the newly identified genes may be related, respectively, to the enzyme involved in cholesterol synthesis and to the process of neuronal cell death.