AGGREGATION OF BETA-AMYLOID PEPTIDE IS PROMOTED BY MEMBRANE PHOSPHOLIPID METABOLITES ELEVATED IN ALZHEIMERS-DISEASE BRAIN

Increased amounts of beta-amyloid (A beta) peptide deposits are found in Alzheimer's disease brain. These amyloid deposits have been implica ted in the pathophysiology of this common dementing illness. A beta pe ptides have been shown to be toxic to neurons in cell culture, and thi s toxicity is critically dependent on the aggregation of the peptide i nto cross-beta-pleated sheet fibrils, Also, in vivo and postmortem NMR studies have shown changes in certain brain membrane phospholipid met abolites in normal aging and more extensive alterations in patients wi th Alzheimer's disease. The finding that membrane phospholipids affect the aggregation of A beta suggests that the abnormalities in membrane metabolism found in Alzheimer's disease could affect the deposition o f A beta in vivo. Therefore, we examined the effect of membrane phosph olipid metabolites that are altered in Alzheimer's disease brain on th e aggregation of A beta(1-40) using a light scattering method. Certain metabolites (glycerophosphocholine, glycerophosphoethanolamine, and a lpha-glycerophosphate) augment the aggregation of A beta. Other membra ne phospholipid metabolites (phosphocholine, phosphoethanolamine, and inositol-1-phosphate) have no effect. We conclude that increased membr ane phospholipid metabolite concentrations may play a role in the depo sition of A beta seen in normal aging and the even greater deposition of A beta observed in Alzheimer's disease.