An integrated approach of genetic epidemiology and molecular genetics in the study of Alzheimer dementia and related phenotypes.

This project aims to contribute to a better understanding of the genetic etiology of complex forms of Alzheimer dementia by means of genetic-epidemiological and molecular genetic techniques. This will help in identifying molecular mechanisms that can serve as targets for early detection, prevention and treatment of this common and incurable disease. High-throughput association studies (both genome-wide and focused on biological pathways) and intermediary or endophenotypes will be performed in a well-characterized study population with sufficient statistical power. Translation of findings to prodromal stages of AD will point out which factors are already of relevance early in the pathological cascade. These factors might find use as early predictors. Pathway analysis will identify subgroups with an increased epidemiological risk profile. In addition, we will assess if these prognostic markers affect easily measurable quantitative traits, e.g. in an integrated study of genome wide genotype data and differential protein expression in a proteomics study. If a correlation can be demonstrated, this trait can be used as a biomarker specific to the disease process. In addition we aim to identify genetic factors that modify onset age, to find novel targets for treatment, to delay or prevent the pathological cascade.

Keywords:PROTEOMICS, ALZHEIMER'S DISEASE, EPIDEMIOLOGY, GENES, GENETIC ASSOCIATION STUDIES

Disciplines:Genetics, Systems biology, Molecular and cell biology, Neurosciences, Public health care, Public health sciences, Public health services, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing