Alzheimer and beta-amyloid-treated fibroblasts demonstrate a decrease in a memory-associated GTP-binding protein, Cp20.
The two proteins most consistently identified in the brains of patients with Alzheimer disease (AD) have been beta-amyloid and tau, whose roles in the physiology or pathophysiology of brain cells are not fully understood. To identify other protein(s) involved in AD that have been implicated in physiological contexts, we undertook to analyze a specific memory-associated protein, Cp20, in fibroblasts from AD and control donors. Cp20, a GTP-binding protein that is a member of the ADP-ribosylation factor family, was significantly decreased in fibroblasts from AD patients. Normal control fibroblasts exposed to 10 nM beta-amyloid, the same concentration that induced AD-like K+ changes in control fibroblasts, showed a similar decrease in Cp20. Since it has been previously demonstrated that Cp20 is a potent regulator of K+ channels, these findings suggest that changes in this memory-associated protein may explain previously observed differences in AD K+ channels and suggest a pathophysiologic involvement linked to soluble beta-amyloid metabolism that could contribute to the characteristic memory loss of AD.
Kim
C S
CS
Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Han
Y F
YF
Etcheberrigaray
R
R
Nelson
T J
TJ
Olds
J L
JL
Yoshioka
T
T
Alkon
D L
DL
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008568:Memory; D051379:Mice / Q000276:immunology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D012867:Skin / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D015221:Potassium Channels; D019204:GTP-Binding Proteins; D011188:Potassium