Toward a molecular etiology of Alzheimer's disease.
Recent progress in the biochemical characterization of Alzheimer's disease (AD) neuropathology has led to the proposal of three hypotheses for the molecular etiology of AD. One focuses on calcium-activated neutral proteases or calpains (Nixon, 1989). Another focuses on protein phosphorylation (Saitoh & Iimoto, 1989). A third is centered on altered phospholipid metabolism (Pettegrew, 1989). Interestingly, all three hypotheses are mutually compatible, involving closely interlocking biochemical systems. Disturbances in any one of these systems might result in the same type of neuropathology, consistent with suggestions that AD could have multiple etiologies. Future investigations of the function and interrelation of these systems in the central nervous system in general and at the synaptic junction in particular are likely to have significant bearing on our understanding of AD.
Banner
C
C
Neuroscience and Neuropsychology of Aging, National Institute on Aging, Bethesda, Maryland.
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics; D001921:Brain / Q000473:pathology; D002118:Calcium / Q000502:physiology; D002154:Calpain / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D009454:Neurofibrils / Q000648:ultrastructure; D010743:Phospholipids / Q000235:genetics; D011480:Protease Inhibitors / Q000378:metabolism
D016229:Amyloid beta-Peptides; D007381:Intermediate Filament Proteins; D010743:Phospholipids; D011480:Protease Inhibitors; D010450:Endopeptidases; D002154:Calpain; D002118:Calcium