engleski

Gangliosides of non-neural tissues in dementia of Alzheimer's type and Down's syndrome

The majority of biochemical disorders in neural and non-neural tissues in Alzheimer's disease (AD) has consequences on cell membrane structure and function. Previous studies showed significant quantitative and qualitative changes of gangliosides (GG) in AD brains explained mostly as the result of neuronal cell loss and glial response, but also possible disorder/acceleration of GG degradation. As GG are incorporated in all types of cell membranes, the hypothesis of this study was that similar metabolic disorder of GG may exist in non-neural tissues in AD. The study was performed on available periperal tissues: skin fibroblasts derived from individuals with neuropathologically confirmed diagnosis of AD and individuals with Down's syndrome (DS) in comparison with age-matched control fibroblasts; leukocytes and serum from individuals with clinical diagnosis of dementia of the Alzheimer's type (DAT, N=19) and DS (N=21) in comparison with age-matched controls (C, N=26). The results showed: (1) statistically significant increase in beta-galactosidase activity in DAT and DS leukocytes and skin fibroblasts, while there were no significant changes in activities of several other lysosomal enzymes of GG degradation; (2) metabolic labelling with 14C-galactose showed increase in total radioactivity incorporation in glycosphingolipid fraction of almost all DS and AD cultures of skin fibroblasts; also, metabolic turnover of glycosphingolipids was greater in fetal Down than in age-matched control fibroblasts; (3) no changes in composition and content of serum gangliosides in DAT and DS samples in comparison with control samples. In conclusion, the results of this study indicate probable disorder of GG metabolism (accelerated ganglioside degradation) in analyzed AD and DS non-neural tissues, and are challenging for our further investigation and understanding of glycosphingolipid metabolism in mentioned diseases.

gangliosides; metabolism; non-neural tissues; dementia of the Alzheimer's type; Down's syndrome

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