Breakdown of membrane phospholipids in Alzheimer disease. Involvement of excitatory amino acid receptors.

Membrane phospholipids are not only essential membrane constituents but also determine many membrane functions and integrity. Normal receptor function, signal transduction, and transport of essential substrates depend strongly on normal membrane phospholipid metabolism. Studies of plasma membrane phospholipid composition have indicated that ethanolamine glycerophospholipids decrease, whereas serine glycerophospholipids increase significantly, in Alzheimer disease (AD). The release of arachidonate from the sn-2 position of glycerophospholipids is catalyzed by phospholipases and lipases. These enzymes are coupled to EAA receptors. Overstimulation of these receptors may be involved in abnormal calcium homeostasis, degradation of membrane phospholipids, and the accumulation of free fatty acids, prostaglandins, and lipid peroxides. Accumulation of the mentioned metabolites, as well as abnormalities in signal transduction owing to stimulation of lipases and phospholipases, may be involved in the pathogenesis of the neurodegeneration in AD.