| Abstract |
Understanding the genetics of Alzheimer's disease is one of the best ways of improving our knowledge of the biology underpinning the disease. Genes are thought to account for around 80% of disease risk. Advances in the field of biomedical genetics have allowed the identification of 26 genes that act to increase a person's risk of developing disease. However, it is believed that there are at least the same number of genes that also contribute to disease risk are yet to be discovered. To identify new disease related genes substantial additional efforts are required. It is particularly important to maximise sample numbers; studies of other complex genetic diseases have shown that the number of disease genes a study can identify increases with the sample size of the study. Our primary objective is therefore to increase the number of Alzheimer's disease samples with genetic data to identify new risk genes for disease. We will achieve this via the creation of a European Alzheimer's Disease DNA BioBank (EADB). We have identified a European cohort of 31,911 AD cases (of which 24,049 have no genetic data) and 40,802 controls (of which 15,638 have no genetic data) from 11 countries. We will undertake genotyping of these 39,687 samples with no genetic data and analyse the new data along with existing genetic data via standard methods. This study plan will allow us to identify new Alzheimer's disease risk genes and the biological pathways in which these genes function. This initiative will increase the number of Alzheimer's disease samples available for genetic studies in Europe by more than 4-fold and worldwide by almost 2-fold. In parallel, the EADB will collect samples from Europe's largest cohort of mild cognitive impairment cases, with a view to identifying genes that change the rate of disease progression and cognitive decline. We have available to us 9,109 mild cognitive impairment cases (of which 6,952 have no genetic data). The cohort includes data on conversion to Alzheimer's disease, cognitive and non-cognitive parameters, cerebrospinal fluid proteins and brain imaging. The identification of genes that are functional in pathways that act to modify Alzheimer's disease risk and increase the rate of disease progression, or increase cognitive decline in mild cognitive impairment, is essential to allow the development and testing of novel treatments. |