Age-associated biochemical changes, Alzheimer’s disease and neuroprotection

Age is the central risk factor in the pathogenesis of the majority of Alzheimer’s disease cases. The analysis of the molecular interplay between the basic mechanisms of cellular aging and the Alzheimer-associated pathobiochemical changes may lead to a better understanding of the pathogenesis of this detrimental disorder. Employing primary human fibroblast cultures from biopsy material of controls and presenilin–1 mutants the cellular processing of the amyloid precursor protein (APP) has been investigated. Indeed, the biochemical changes that occurred during the process of replicative senescence in these fibroblast cultures have a dramatic impact on the processing of APP. Moreover the oxidative stress that is accumulating over the aging process may also influence APP processing perhaps through an effect on the membrane subdomains. A better understanding of the influence of age at the cellular and molecular level of aging at a cellular and molecular level on Alzheimer’s associated biochemistry may lead to novel concepts of prevention and therapy. Moreover it is well known that during aging a variety of neuroprotective factors are depleted further supporting the idea that the aging process is rendering nerve cells more vulnerable to disease associated insults. A better understanding of the age process itself at a cellular and molecular level will help to understand age-associated neurodegenerative disorders.

The Alzheimer and aging projects of the Behl group are supported by the Deutsche Alzheimer Stiftung, the Peter Beate Heller Stiftung and the Deutsche Forschungsgemeinschaft (BE 1475/4–1).