[Pathogenesis of Alzheimer's disease: molecular and cellular mechanisms]

Alzheimer's disease is worldwide the leading cause of dementia in the elderly. Senile plaques and neurofibrillary tangles are together with neuronal loss and cortical atrophy characteristic neuropathological features of the disease. Senile plaques contain beta-amyloid (Abeta) peptide which is produced by cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. Neurofibrillary tangles are twisted helicoidal strands of hyperphosphorylated tau protein, a microtubule-associated protein. Both pathogenic arms which we describe are interrelated and Abeta deposition seems to potentiate tau pathology. Tangle and plaque formation is influenced by various factors including reciprocal interactions, genetic factors, inflammation and reactive oxygen species. A better understanding of the cellular and molecular cascade which leads to the neuropathological lesions of Alzheimer's disease has led to novel disease-modifying treatment strategies. They yield varying, though encouraging, results and target various stages of the pathological process. Future cooperation between basic, clinical and pharmacological research should allow the development in a foreseeable future of strategies that can halt, or even prevent, this devastating disorder.