NMDA AND AMPA RECEPTORS IN TRANSGENIC MICE EXPRESSING HUMAN BETA-AMYLOID PROTEIN

The human beta-amyloid protein may play an important, possibly primary , role in the pathogenesis of Alzheimer's disease (AD), and it appears to potentiate the susceptibility of neurons to excitotoxicity. AD is associated with alterations in the N-methyl-o-aspartate (NMDA) and pha -amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) subtypes o f glutamate receptors, and it has been suggested that excitotoxicity m ay play a role in neuronal damage in AD. In this study, we have used q uantitative receptor autoradiography to examine NMDA and AMPA receptor s in transgenic mice that contain the gene for the carboxyl-terminal 1 00 amino acids of the human amyloid precursor protein, beginning with the beta-amyloid region, which is under the control of the JC viral ea rly region promoter. Reverse transcriptase-polymerase chain reaction c onfirmed that the brains of transgenic mice expressed beta-amyloid mRN A and that control mice did not. NMDA receptors, assessed with [H-3]MK -801, were unchanged in the transgenic compared with the control mice. In the transgenic mice, there were no significant changes in [H-3]AMP A receptor binding compared with controls. This study represents the f irst attempt to evaluate in transgenic mice the in vivo interaction be tween beta-amyloid expression and excitatory amino acid receptors.