Molecular mechanisms of memory and the pathophysiology of Alzheimer's disease.
Research on molecular and biophysical mechanisms of associative learning and memory storage identified a number of key elements that are phylogenetically conserved. In both vertebrates and invertebrates, K+ channels, PKC, Cp20, and intracellular Ca2+ regulation play a fundamental role in memory mechanisms. Because memory loss is the hallmark and perhaps the earliest sign of Alzheimer's disease, we hypothesized that these normal memory mechanisms might be altered in AD. With the use of a variety of experimental methodologies, our results revealed that one of the critical elements in memory storage, K+ channels, are dysfunctional in AD fibroblasts. Moreover, beta-amyloid induced the same K+ dysfunction in normal cells. Intracellular Ca2+ release, also associated with molecular memory mechanisms, was found altered in fibroblasts from patients with AD. The results therefore strongly suggest that biophysical and molecular mechanisms of associative learning could be altered in AD and that they may contribute to the memory loss observed early in the disease.
Etcheberrigaray
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Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Gibson
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Alkon
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D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D015221:Potassium Channels / Q000502:physiology
D016229:Amyloid beta-Peptides; D015221:Potassium Channels; D002118:Calcium