The two proteins most consistently identified in the brains of patients with Alzheimer disease (AD) have been ,B-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, Cp2O, in fibroblasts from AD and control donors. Cp2O, 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 ,B-amyloid, the same concentration that induced AD-like K+ changes in control fibroblasts, showed a similar decrease in Cp2O. Since