Evidence for lipid alterations in lipid rafts from alzheimer's disease human brain

Lipid rafts are membrane microdomains involved in cell signalling and characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids. In this study, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) cell membranes and analyzed their lipid composition. Compared to non-AD brains, lipid rafts from AD brains displayed low levels of n-3 long chain highly unsaturated fatty acids (HUFA) specially 22: 6n-3 (docosahexaenoic acid) and n-9 monoenes (specially 18: 1n-9, oleic acid). Changes in lipid structure of AD lipid rafts also involved significant reductions in the unsaturation and peroxidability indexes as well as increased unsaturated/cholesterol unsaturated/sphingomyelin and saturates/n-3 HUFA ratios. These results indicate that the mechanisms preserving lipid raft order and viscosity in normal frontal cortex are disrupted in AD brains, which partially might explain the abnormal intracellular signalling mechanisms observed during AD.