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Project

Next-generation genetics of early-onset dementia to increase our appreciation of the molecular signatures of dementia.

There is a current paucity of effective prophylactic treatments for neurodegenerative dementia disorders and as such they represent one of the major classes of widespread diseases with increasing mortality rates in the developed world. Drug development programs have faced numerous problems. The clinical and biological complexity of dementia has long been underestimated. Evidence increases that patients with the same clinical symptoms develop disease through different biological processes. This implicates that intervention trials should be directed towards subgroups of patients that share the same molecular signature of disease biology. The proposed PhD project aims to further elucidate the genetic etiology and molecular signatures of dementia through the identification of novel genes and genetic disease modifiers. A better understanding of the molecular complexity of dementia will improve classification of patients based on their molecular disease signatures rather than on clinico-pathological symptomatology, which is expected to drastically improve development of effective diagnostic tools, biomarkers and targeted therapies.We will apply advanced genetic profiling strategies for novel gene discovery, including whole exome and gene panel sequencing focusing on the subgroup of early-onset dementia (EOD) patients. Because EOD patients suffer from a disease of the aging brain at a relatively young age, they have an extreme presentation of the disease and as such are expected to have a strong genetic heritage. Study of this subgroup of dementia patients will therefore more likely lead to identification of novel genes and molecular pathways. The research will build on an impressive collection of >4000 patients ascertained within the European Early-Onset Dementia consortium. Making use of these powerful genomic approaches in selected patient cohorts with strong genetic heritage, we aim to identify novel key genes and proteins and enhance our knowledge of the molecular signatures of neurodegenerative dementia. These signatures will be instrumental in pinpointing diagnostic biomarkers and drug targets for therapy development, will allow more accurate stratification of patient cohorts for follow-up translational research and clinical trials, and ultimately offer better perspectives for patients and families affected by dementia.
Date:1 Oct 2015 →  30 Sep 2019
Keywords:DEMENTIA, EARLY-ONSET DEMENTIA, GENETIC MODIFIER, GENETIC RISK FACTORS
Disciplines:Genetics, Systems biology, Molecular and cell biology, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing