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 of this neuropathology. Recent progress in understanding mechanisms for AD results from the study of amyloid precursor protein (APP) metabolism and the involvement of senile plaque-associated proteins. In addition to the amyloid cascade hypothesis, alternative schemes emerge, in which the amyloid peptide is not the primary effector of the disease. Perturbations of vesicular trafficking, the cytoskeletal network, and membrane cholesterol distribution could be central events. Furthermore, since the physiological role of APP, presenilins, and apolipoprotein E in the central nervous system are not completely understood, their involvement in AD etiology remains speculative. New actors have to be found to try to explain sporadic cases and non-elucidated familial cases.
Drouet
B
B
INSERM U-505, Institut des Cordeliers, Paris, France.
Pinçon-Raymond
M
M
Chambaz
J
J
Pillot
T
T
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009336:Necrosis; D009457:Neuroglia / Q000473:pathology; D053764:Presenilin-1; D053766:Presenilin-2; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D016875:tau Proteins; D002784:Cholesterol