REGIONAL DECREASES OF FREE D-ASPARTATE LEVELS IN ALZHEIMERS-DISEASE

N-methyl-D-aspartate (NMDA) receptors have been shown to be involved i n learning and memory processes. In Alzheimer's disease, there is a re duction of NMDA receptors. Since D-aspartate is an endogenous agonist for the NMDA receptor, we hypothesised that if there are reduced level s of this amino acid in the Alzheimer's brain, this could raise the re duction 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-aspar tate levels in post-mortem human brain samples from patients with Alzh eimer's disease (AD) (n = 5) and age-matched controls (n = 5) were det ermined. We found that the levels of D-aspartate are significantly low er in Alzheimer's patients compared to controls (range: from -35 to -4 7%; P < 0.01). However, no differences were found in the cerebellum, a region spared from the neuropathological changes of AD. These data su ggest that decreased levels of D-aspartate could contribute to a lower NMDA receptor function and consequently contribute to the memory defi cits seen in AD (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.