Enhanced GM1 ganglioside catabolism in cultured fibroblasts from Alzheimer patients

The metabolic processing of GM1 ganglioside, exogenously administered to cultured skin fibroblasts, was investigated on cells obtained from patients affected with Alzheimer disease, in comparison with age-matched control subjects. Cultured fibroblasts were incubated with GM1 ganglioside, [H-3]-radiolabelled at the sphingosine moiety. It was observed that the extent of tritiated GM2 and GM3 ganglioside formation was higher in AD fibroblasts than in control cells. The activity of acidic beta-D-galactosidase, responsible of GM1 hydrolysis to GM2 within lysosomes, assayed in vitro on cell lysates, was increased in AD fibroblasts in comparison with control cells. These data suggest that up-regulation of lysosomal enzymes could be responsible of the enhanced GM1 catabolism in AD fibroblasts. Finally, it was found that the extent of GM1 hydrolysis in AD fibroblasts was inversely correlated with the mini-mental score index of patients. The increased hydrolysis rate of sphingolipids could be taken as peripheral hallmark of Alzheimer's disease patients. (c) 2004 Elsevier Inc. All rights reserved.