Metabolic alterations in postmortem Alzheimer's disease brain are exaggerated by Apo-E4

Alterations in phospholipid metabolites are a characteristic abnormality of Alzheimers disease (AD). Many of these alterations have been demonstrated by magnetic resonance spectroscopy (MRS) studies of postmortem tissue. Phos phodiesters appear to be elevated late in the disease and phosphomonoesters appear to be elevated early in the disease and then decrease. Second to ag ing, the most robust risk factor for AD identified to date is the presence of the E4 allele of apolipoprotein-E (Apo-E). Because apolipoproteins are i ntimately involved in lipid metabolism, this study was performed to determi ne if the presence of the Apo-E4 allele affects the abnormalities in phosph olipid metabolites in AD brain. Perchloric acid extracts from 12 Apo-E 3/3, 31 3/4, 6 4/4 AD brains and 5 Apo-E 3/3 control brains were studied by bot h proton magnetic resonance spectroscopy and phosphorus-31 magnetic resonan ce spectroscopy. When the E4-positive AD samples were compared with the 3/3 AD samples, an exaggeration in both phosphomonoester and phosphodiester ab normalities was observed. The decrease in N-acetyl-L-aspartate (NAA) was al so exaggerated. These results suggest membrane phospholipid metabolite alte rations observed in AD are more severe in the presence of the Apo-E4 allele . (C) 1999 Elsevier Science Inc.