Genetic risk factors for Alzheimers's disease: a search for pathomechanisms.

Alzheimer's disease (AD) is the most common form of dementia. By pooling many study populations and thus increasing statistical power, recent international genome wide association studies have uncovered 10 novel genes associated with Alzheimer's risk (CLU, CR1, PICALM, BIN1, ABCA7, CD2AP, CD33, EPHA1, MS4A4E and MS4A6A). The principal aim of this project is to identify and extensively investigate novel genetic risk variants that might explain pieces of the missing heritability of AD. We will use next-generation sequencing technology to investigate the entire novel AD genes, including up- and downstream regulatory regions, in our prospective Flanders-Belgian study population (currently 1263AD patients and 1029 control individuals). The genetic follow-up of these AD genes consists of 5 tiers: Identification of a common genetic variant that explains the observed association between the gene and AD, in a high-density SNP-based analysis of the Flanders-Belgian AD study population. Exploration of the presence of both rare variants and structural variations in the novel AD genes. We will also investigate the possibility of genetic interactions between different genes because of the complexity of late onset AD. Further we will perform genotype-phenotype correlation studies with phenotypes ranging from biomarker profiles in CSF, plasma or serum to clinical phenotypes. Lastly we will investigate the functional effect of the associated variations.

Keywords:ALZHEIMER'S DISEASE, GENETIC RISK FACTORS

Disciplines:Genetics, Systems biology, Molecular and cell biology