Regional decreases of free D-aspartate levels in Alzheimer's disease

Abstract

N-methyl-D-aspartate (NMDA) receptors have been shown to be involved in learning and memory processes. In Alzheimer's disease, there is a reduction of NMDA receptors. Since D-aspartate is an endogenous agonist for the NMDA receptor, we hypothesised that if there are reduced levels of this amino acid in the Alzheimer's brain, this could raise the reduction of NMDA receptor signal transduction system and contribute to the marked memory deficits seen in these patients. Therefore, using a chromatographic HPLC method, the regional distribution of free D-aspartate levels in post-mortem human brain samples from patients with Alzheimer's disease (AD) (n = 5) and age-matched controls (n = 5) were determined. We found that the levels of D-aspartate are significantly lower in Alzheimer's patients compared to controls (range: from -35 to -47%; P < 0.01). However, no differences were found in the cerebellum, a region spared from the neuropathological changes of AD. These data suggest that decreased levels of D-aspartate could contribute to a lower NMDA receptor function and consequently contribute to the memory deficits seen in AD.