Alzheimer disease: protein-protein interaction and oxidative stress.

Abstract

Alzheimer disease, the most prevalent dementia of the aged, is defined by the concurrence of two filamentous brain lesions: neurofibrillary tangles and senile plaques. The lesions are temporally and spatially correlated to each other and to cognitive impairment suggesting that is a interaction between neurofibrillary tangles and senile plaques that might play a role in disease pathogenesis. Here we present findings demonstrating specific interactions between the major protein components of the lesions. Such an interaction is likely important to lesion genesis and to the overall cognitive deficits seen clinically. Also important are forces that stabilize and cement abnormal interactions and protect them form removal. Oxidative post-translational modifications is probably one of the major mediators that by disrupting cellular homeostatic balance both promotes abnormal interactions and makes them resistant to proteolytic removal. Overall, these findings support the view that the lesions of Alzheimer disease are intimately involved in neuronal destructions.