Analysis of the core components of Alzheimer paired helical filaments A gas chromatography/mass spectrometry characterization of fatty acids, carbohydrates and long-chain bases

Abstract

We have carried out a fatty acid and carbohydrate compositional analysis of the protease-resistant core of paired helical filaments (prcPHF) isolated from six Alzheimer's diseased brains. Fatty acids, long-chain bases and monosaccharides were characterized by gas chromatography/mass spectrometry (GC/MS) of fatty acid methyl esters, trimethylsilylated long-chain bases, peracetylated alditol acetates and trimethylsilyl methyl glycosides. Glucose and mannose were found to be the only carbohydrate components. Four of the six prcPHF samples contained only glucose while the remaining two samples contained between 30–40% mannose in addition to glucose. None of the samples were found to contain either hydroxylated fatty acids or long-chain bases. The average fatty acid profile of prcPHF was highest in stearic (C18:0) and palmitic acids (C16:0) with less than 10% unsaturated fatty acids. By comparing the carbohydrate and lipid composition of prcPHF to similar data for other brain glycolipids, it was determined that prcPHF is a unique glycolipid, distinct from cerebrosides, gangliosides or brain phospholipids. The fatty acid and carbohydrate composition of a glycolipid isolated from a population of normal brains according to the prcPHF protocol was found be identical to that of prcPHF glycolipid. It is possible that subtle differences in structure or indigenous factors are responsible for the initiation of PHF formation in vivo.