engleski

Activities of several lysosomal enzymes involved in ganglioside catabolism in leukocytes and skin fibroblasts derived from individuals with diagnosis of dementia of the Alzheimer's type and Down's syndrome

This study is based on several facts: (1) previously shown specific quantitative and qualitative changes of brain gangliosides in Alzheimer's disease (AD), reflecting brain atrophy, neuronal cell loss and reactive gliosis, but also discussed possibility of accelerated lysosomal degradation of gangliosides during pathologic processes in AD brain; (2) hypothesized systemic character of AD; (3) cell membrane structure and function disorders found in AD neural and non-neural tissue; (4) importance and nature of gangliosides incorporated in all animal cell plasma membranes. The aim of the study was to show whether there are changes in ganglioside metabolism in available peripheral tissues in AD and Down's syndrome (DS). The study was performed on: (a) leukocytes isolated from individuals with clinical diagnosis of the dementia of the Alzheimer's type (DAT, N=19) and Down's syndrome (N=21) in comparison with age-matched controls (CDAT, N=12; CDS, N=17); and (b) cultures of skin fibroblasts derived from individuals with neuropathologically confirmed diagnosis of AD and age-matched control fibroblasts and skin fibroblasts from individuals with Down's syndrome with their age-matched controls. Activities of beta-galactosidase, beta-hexosaminidase, and beta-hexosaminidase A were determined in homogenates of leukocytes and fibroblasts by fluorometry using methylumbelliferon substrates; activity of arylsulphatase A (involved in degradation of sulphatides) in same material was determined by spectrophotometry using chromogenic substrate; the activites of enzymes were expressed as nmol (substrate)/mg proteinxh. The results showed: (1) statistically singificant increase in beta-galactosidase activity in both DAT leukocytes in comparison with age-matched control group (P0.01, Student t-test) and DS leukocytes when compared with controls (P0.05, Student t-test); (2) no significant changes in activity of other enzymes analyzed in DAT, DS and control leukocytes; (3) slight increase in activities of beta-galactosidase, beta-hexosaminidase, and beta-hexosaminidase A, and slightly decreased activity of arylsulphatase A in control leukocytes with ageing; (4) increase in beta-galactosidase and beta-hexosaminidase activity in both AD and DS skin fibroblasts in comparison with age-matched control fibroblasts. In conclusion, there may exist a disorder in ganglioside metabolism, indicating accelerated lysosomal degradation of gangliosides, in AD and DS peripheral cells and for enzymes analyzed in this study.

lysosomal enzymes; ganglioside degradation; peripheral tissues; dementia of the Alzheimer's type; Down's syndrome

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