Chapter 11 High Performance Liquid Chromatography of Glycosphingolipids in Brain Disease

Abstract

Publisher Summary This chapter presents a high pressure liquid chromatography (HPLC) procedure that provides the necessary sensitivity, resolution, and reproducibility to permit the determination of glucocerebroside levels in specific brain regions and to correlate the findings with the neuropathology. The microanalytical HPLC procedure for glucocerebroside permits such analyses on very small (a few mg wet weight) quantities of specific brain regions. Nine separate brain regions from types 2 and 3 Gaucher's disease are analyzed by HPLC of their perbenzoylated glucocerebrosides. In both types, the greatest glucocerebroside accumulation, when compared t o controls, is found in the occipital cortex, with lesser amounts in the temporal and frontal areas. The cerebellar cortex, corpus striatum, and thalmus of the Gaucher brains mildly increases levels of glucocerebroside, especially when the values are expressed as a percentage of the total non-hydroxyl fatty acid cerebrosides. The type-2 brain stem structures also shows as light elevation of glucocerebroside over controls when the data is again expressed as the percentage of the total nonhydroxy fatty acid cerebrosides. The histopathological abnormalities in the type-2 Gaucher brain correlate with elevated tissue glucocerebroside levels. Type-3 Gaucher brain shows no pathological changes but the glucocerebroside accumulation is similar to that seen in type 2 brain.