Alzheimer disease paired helical filament core structures contain glycolipid

Abstract

The core structures of sodium dodecyl sulfate extracted, pronase digested paired helical filaments of Alzheimer disease were solubilized by heating in dimethyl sulfoxide. Electron microscopy revealed that after heating in dimethyl sulfoxide, intact paired helical filaments were no longer present in the dimethyl sulfoxide soluble fractions or in the insoluble lipofuscin-containing fractions. Enzyme-linked immunosorbant assays of the various fractions with the monospecific antibody A128 to paired helical filaments demonstrated 96% of the immunoreactivity to be in the dimethyl sulfoxide soluble fraction, and only 4% in the dimethyl sulfoxide insoluble fractions. Lyophilization of the dimethyl sulfoxide soluble supernatant and resuspension in water failed to reassociate the paired helical filaments, but did result in an insoluble precipitate. Analysis of the dimethyl sulfoxide solubilized paired helical filament fraction by nuclear magnetic resonance revealed it to be composed of glycolipid in a form that was distinct from similar fractions isolated from normal aged control brains. The aggregation of an altered glycolipid to form paired helical filaments in Alzheimer disease could explain their insolubility.