Genetic risk for frontotemporal lobar degeneration: A genome-wide approach.

Aging of the global population has caused dementia to become one of the leading causes of morbidity and mortality. Notwithstanding there is still no therapy available that can cure or prevent dementia. For this research project our focus is on frontotemporal lobar degeneration (FTLD). FTLD is after Alzheimer's disease one of the major causes of dementia, accounting for 5 to 10% of all dementia patients and up to 20% of patients younger than 65 years. Up to up to 40% of FTLD patients have a positive family history of dementia. In the last few years major progress has been made in dissecting the genetic etiology of FTLD. Four genes have already been identified for autosomal dominant FTLD ¿ MAPT, PGRN, CHMP2B, VCP ¿ explaining about 20% of patients. Despite these efforts the majority of FTLD patients still remain unexplained. It is expected that in these patients the cause of the disease is complex in nature, i.e. the result of interplay between genetic and environmental factors. The aim of this research project is to identify such genetic factors that contribute to the risk of developing FTLD in a significant fraction of patients trough a genome-wide association approach. To this extent we will invest in the assembly of an extended, well-documented collection of biomaterials ¿ DNA/RNA, plasma/serum, EBV cell lines, fibroblasts, CSF, brain material ¿ from FTLD patients, families, and control individuals to create a powerful tool to undertake genome-wide association studies. This project will allow extended clinical, pathological, and biologic information to be combined with whole-genome information which will in turn offer the potential to increase our understanding of the pathogenesis of FTLD and provide targets for early diagnosis, prevention and therapy.

Keywords:DEMENTIA, FRONTOTEMPORAL LOBAR DEGENERATION, MOLECULAR GENETICS

Disciplines:Microbiology, Systems biology, Neurosciences, Veterinary medicine, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing