Molecular basis of Alzheimer's disease

Despite an exponential production of data, Alzheimer's disease (AD) remains an enigma. Unresolved questions persist in the face of the heterogeneity o f this neuropathology. Recent progress in understanding mechanisms for AD r esults from the study of amyloid precursor protein (APP) metabolism and the involvement of senile plaque-associated proteins. In addition to the amylo id cascade hypothesis, alternative. schemes emerge, in which the amyloid pe ptide is not the primary effector of the disease. Perturbations of vesicula r trafficking, the cytoskeletal network, and membrane cholesterol distribut ion could be central events. Furthermore, since the physiological role of A PP, presenilins, and apolipoprotein E in the central nervous system are not completely understood, their involvement in AD etiology remains speculativ e. New actors have to be found to try to explain sporadic cases and non-elu cidated familial cases.