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In Alzheimer's disease, all ganglio-series gangliosides (GM1, GD1a, GD1b and GT1b) were found to be decreased in temporal and frontal cortex, and nucleus basalis of Meynert. In addition, in Alzheimer's disease simple gangliosides (GM2, GM3) were elevated in frontal and parietal cortex, possibly correlating to accelerated lysosomal degradation of gangliosides and/or astrogliosis occurring during neuronal death.

In this study, brain gangliosides in prenatal and postnatal human life and Alzheimer's disease were analyzed. Immunohistochemically, the presence of the "c"-series of gangliosides (GQ1c) was only registered in the embryonic brain at 5 weeks of gestation. Biochemical results indicated a two-fold increase in ganglioside concentration in the human cortex between 16 and 22 weeks of gestation. The increasing ganglioside concentration was based on an increasing GD1a ganglioside fraction in all regions analyzed except in the cerebellar cortex, which was characterized by increasing GT1b. During prenatal human development, regional differences in ganglioside composition could only be detected between the cerebrum ("a"-pathway) and the cerebellum ("b"-pathway). Between birth and 20-30 years of age, a cerebral neocortical difference of ganglioside composition occurred, characterized by the lowest GD1a in visual cortex. Analyzing the composition of gangliosides in cortical regions during aging, they were observed to follow region-specific alterations. In the frontal cortex, there was a greater decrease in GD1a and GM1 than in GT1b and GD1b, but in the occipital (visual) cortex there was no change in individual gangliosides. In hippocampus, GD1a moderately decreased, whereas other fractions were stable. In the cerebellar cortex, GD1b and GT1b fractions decreased with aging. In Alzheimer's disease, we found all ganglio-series gangliosides (GM1, GD1a, GD1b, GT1b) to be decreased in regions (temporal and frontal cortex and nucleus basalis of Meynert) involved in pathogenesis of disease. In addition, in Alzheimer's disease we found simple gangliosides (GN2, GM3) to be elevated in the frontal and parietal cortex, which might correlate accelerated lysosomal degradation of gangliosides and/or astrogliosis occurring during neuronal death.

In this study, brain gangliosides of patients with Alzheimer's disease (AD, N = 5) were analyzed and compared with control human brains (C, N = 3). Gangliosides were analyzed in seven brain regions: cerebral cortex (frontal, parietal, temporal and occipital), hippocampus, basal telencephalon and frontal white matter. The results demonstrated gangliosides to be decreased in the majority of regions analyzed, however, a significant decrease in gangliosides (nmol LBSA/mg proteins or g fresh weight) in frontal cortex and white matter (P less than 0.05) was recorded. When gangliosides were expressed in nmol LBSA/mg DNA (deoxyribonucleic acid), their basal telencephalon, suggesting that high astroglial proliferation might have concealed the real neuronal degeneration. In the ganglioside composition, all human brain regions contained moderately decreased ganglio-series gangliosides (GT1b, GD1b, GD1a, GM1) but a statistically significant decrease was detected in frontal cortex, and white matter (nmol LBSA/g fresh weight) or frontal cortex, temporal cortex and basal telencephalon (nmol LBSA/mg DNA). In addition, frontal and parietal cortex also showed elevated concentration (nmol LBSA/g fresh weight) of simple gangliosides (GM2, GM3, GM4, GD3). A decreased concentration of ganglio-series gangliosides in Alzheimer's disease correlates with degeneration of cortical neurons. However, elevation of simple gangliosides in frontal and parietal cortex may correlate with: (a) an accelerated lysosomal degradation of gangliosides occurring during neuronal death (GM2); (b) astrogliosis (GM3 and GD3); and (c) activation of oligodendrocytes (GM4). The fact that gangliosides are altered in Alzheimer's disease might be important for better understanding of the pathogenesis of the disease.

The results demonstrated a statistically significant decrease of ganglio-series gangliosides (GTlb, GDlb, GDla, GMl, nmol lipid-bound sialic acid/mg DNA) in frontal and temporal cortex and basal telencephalon of brains with Alzheimer's disease (AD) in comparison to control brains (P less than 0.05). In addition, frontal and parietal cortex also showed somewhat elevated concentrations of simple gangliosides (GM2, GM3, GM4). Changes in gangliosides in seven regions of human brains with AD analyzed, except of the temporal cortex, did not significantly differ in the "a"/"b" ratio (GDla + GMl/GDlb + GTlb) of ganglioside composition in comparison to control brains. In temporal cortex, an decrease of "a"/"b" ratio on the accounts of more decreased GDla and GMl than GDlb and GTlb was found. A decreased concentration of ganglio-series gangliosides in AD probably correlates with degeneration of cortical neurons. However, elevation of simple gangliosides in frontal and parietal cortex might correlate with an accelerated lysosomal degradation of gangliosides and/or astrogliosis occurring during neuronal death.