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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Neurogenetics of aging: impact of DNA repair on Alzheimer disease

Tildelt: kr 4,1 mill.





2009 - 2013


The genetic background for cognitive loss, dementia and aging processes is poorly described, and multidisciplinary research is needed to increase this knowledge. Alzheimer disease (AD) is by far the most important contributor to cognitive decline and deme ntia worldwide. Incidence may quadruple soon due to an exponentially increase of incidence with age and expected demographic changes if prophylactic theraphy is not introduced. Genetic factors may contribute to 60-80% of disease susceptibility, however, o nly ApoeE4 has been established as a risk factor for the common late-onset form. Oxidative stress and impaired mitochondrial function accompany aging and in particular AD. Non-replacable neurons are particularly vulnerable to oxidative stress and thus dep endent on elaborate defense mechanisms. We hypothesize that impaired base excision repair mechanisms may be predisposing factors for ageing-related brain changes, and constitute risk factors for AD. In order to discover genetic risk factors in AD, this n ew project brings together advanced molecular genetics, advanced imaging and neuropsychology to elucidate these genetic mechanisms in well-characterized AD patients. Merging research efforts from the Centre for Molecular Biology and Neuroscience (CMBN), t he Department of Psychology UiO and the Department of Neurology UiO at AHUS monitor molecular, cognitive and brain morphometry changes as delineated by state-of-the art technology. Healthy volunteers representing normal controls and patients with cognitiv e loss and Alzheimer disease will be correlated with the presence of non-synonymous single nucleotide polymorphisms (nsSNPs) and other changes in genes for base excision repair of DNA. These translational studies will provide new insight into AD pathogene sis and yield novel targets for therapeutic measures.


FRIMEDBIO-Fri prosj.st. med.,helse,biol