i(3)so3-galactosylceramide and Dementia

Topics: Cerebroside-Sulfatase; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 22; Dementia; Galactosylceramidase; Genes, Recessive; Humans; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Lysosomes; Mutation; Sulfoglycosphingolipids

In addition to pathology in the gray matter, there are also abnormalities in the white matter in Alzheimer's disease (AD). Sulfatide species are a class of myelin-specific sphingolipids and are involved in certain diseases of the central nervous system. To assess whether sulfatide content in gray and white matter in human subjects is associated with both the presence of Alzheimer's disease (AD) pathology as well as the stage of dementia, we analyzed the sulfatide content of brain tissue lipid extracts by electrospray ionization mass spectrometry from 22 subjects whose cognitive status at time of death varied from no dementia to very severe dementia. All subjects with dementia had AD pathology. The results demonstrate that: (i) sulfatides were depleted up to 93% in gray matter and up to 58% in white matter from all examined brain regions from AD subjects with very mild dementia, whereas all other major classes of lipid (except plasmalogen) in these subjects were not altered in comparison to those from age-matched subjects with no dementia; (ii) there was no apparent deficiency in the biosynthesis of sulfatides in very mild AD subjects as characterized by the examination of galactocerebroside sulfotransferase activities in post-mortem brain tissues; (iii) the content of ceramides (a class of potential degradation products of sulfatides) was elevated more than three-fold in white matter and peaked at the stage of very mild dementia. The findings demonstrate that a marked decrease in sulfatides is associated with AD pathology even in subjects with very mild dementia and that these changes may be linked with early events in the pathological process of AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Chemistry; Ceramides; Dementia; Disease Progression; Galactosylceramides; Humans; Neuropsychological Tests; Severity of Illness Index; Spectrometry, Mass, Electrospray Ionization; Sphingomyelins; Sulfoglycosphingolipids; Sulfotransferases

The aim of this study was to investigate two putative pathophysiological aspects of the common neurodegenerative disorder frontotemporal dementia (FTD). To this end, cerebrospinal fluid (CSF) levels of tau (total tau) and the light subtype of the neurofilament proteins (NFL) were studied in patients with FTD (n=16) and in age-matched controls (n=16). In addition, serum was analysed for IgG and IgM antibodies to the most common gangliosides and sulfatide in FTD patients (n=13) and in age-matched controls (n=20). The CSF-NFL levels were increased in FTD (1606+/-1151 pg/ml, mean+/-S.D.; P<0.001) compared with controls (308+/-203 pg/ml), whereas the CSF-tau levels were normal. In serum, autoantibody IgG-GA1 was significantly increased in FTD (P<0.05) compared with controls. No correlations were found between the effect parameters and demographic variables in any group. The results of this study suggest that cytoskeleton proteins other than tau are also involved in the pathophysiology of FTD and that autoimmunity may be part of the pathophysiological processes in FTD, as it is believed to be in Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Autoantibodies; Autoimmunity; Dementia; Female; Gangliosides; Humans; Immunoglobulin M; Male; Middle Aged; Neurofilament Proteins; Sulfoglycosphingolipids; tau Proteins

A study was conducted on the fatty acid composition of cerebroside, sulfatide and ganglioside in the brains of 4 cases of Nasu-Hakola disease. The percentage of short carbon chain (C.16-C.18) nonhydroxy fatty acids of sulfatide in the cortex was much higher than that of the control and long-chain (C.24-) fatty acids showed a lower percentage. Sulfatide in the white matter was of the same tendency. The percentage of C.16:0 palmitic acid of ganglioside in the cortex was much larger than that of the control. Referring to the fatty acid composition of lipids in the literature, abnormalities of the fatty acid concentration, namely a high percentage of short-chain fatty acids of sulfatide and ganglioside in the cerebral cortex of the present cases, were confirmed.

Topics: Adult; Axons; Cerebral Cortex; Cerebrosides; Dementia; Fatty Acids; Fatty Acids, Volatile; Female; Galactolipids; Gangliosides; Glycolipids; Humans; Inclusion Bodies; Leukoencephalopathy, Progressive Multifocal; Lipodystrophy; Male; Middle Aged; Myelin Sheath; Sulfoglycosphingolipids