The Alzheimer's plaques, tangles and memory deficits may have a common origin; part I; a calcium deficit hypothesis.
Review of the literature reveals that several biochemical events implicated in the pathology of Alzheimer's disease (AD) are calcium dependent processes. These processes include normal processing of beta-amyloid precursor protein, dephosphorylation and degradation of tau, neurotransmitter release and memory formation. Since all of these processes appear to be inactivated during progression of AD, we propose that a "deficit" of intracellular calcium levels may occur in the early phase of the disease. We also propose several experiments to test this hypothesis. The hypothesis predicts that presenilins most likely act as calcium channels in vivo and that their gene mutations may cause the disease by diminishing the Ca2+ channeling function.
Chen
M
M
Department of Pharmacology and Therapeutics, University of South Florida, College of Medicine, Tampa, Florida, USA. michen@com1.med.usf.edu
D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000187:drug effects; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002118:Calcium / Q000172:deficiency*; D002120:Calcium Channel Agonists / Q000494:pharmacology / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008568:Memory; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D002118:Calcium