100-plus

Some people reach ages well over 100 years with retained mental health, while others develop symptoms of Alzheimers Disease (AD) at 60 years. Currently, there is no cure that prevents or delays dementia onset. The heritability of AD risk is estimated to be 60-80%. Vice versa, extreme old age without dementia often occurs within families, suggesting that the risk to develop dementia is dictated for a large part by our unique constellations of genetic variants. Some of these genetic elements are known, but a large fraction of heritability for AD has not yet been explained. Identification of risk-modulating genetic elements will provide new insights in the molecular processes that associate with changes in cognitive health during ageing. We aim to detect genetic elements associated with AD risk by assessing the genetic variants of a large number of AD cases and controls across all ages. To acquire a resource for protective genetic elements against AD we set up the 100-plus Study, a unique cohort of genomes from cognitively healthy centenarians. Furthermore, as part of a large collaborative effort between Alzheimer researchers, we have access to the largest collection of Alzheimer genetic data world-wide. We aim to identify protective and risk-increasing genetic variants by detecting genetic elements that differentially occur between healthy centenarians and AD patients. These will provide new directions for AD research and druggable targets for treating dementia. Due to the complexity of the genome, the computational power available on Cartesius is a prerequisite for these analyses.