NMDA, AMPA, and benzodiazepine binding site changes in Alzheimer's disease visual cortex

Abstract

Quantitative receptor autoradiography was used to measure the laminar distribution of [3H]glycine and [3H]glutamate binding to the N-methyl-D-aspartate (NMDA) receptor complex, [3H]D,L-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding to the AMPA receptor, and [3H]flunitrazepam binding to the benzodiazepine (BDZ) receptor in three areas of visual cortex in control and Alzheimer's disease (AD) postmortem human brains (primary or striate visual cortex, visual association cortex, and higher-order visual association cortex, corresponding to Brodmami Areas 17, 18, and 21, respectively). In Area 17, binding to the NMDA, AMPA, and BDZ receptors was not significantly altered in the AD brains (except in layer VI for [3H]glycine and layer III for [3H]AMPA, where binding was reduced in the AD brains). Ligand binding to the two EAA receptors in Area 18 was, however significantly reduced in the AD brains (layers I through III for [3h]glycine and layers III through VI for [3H]AMPA). In Area 21, binding to both the NMDA and BDZ receptors but not to the AMPA receptor, was significantly reduced in almost all laminae of the AD brains (layers I through VI for [3H]glycine and layers I through V for [3H]flunitrazepam). This hierarchical pattern of laminar binding loss with increasing complexity of association visual cortices is consistent with the increasing numbers of neurofibrillary tangles found in those areas, implicating NMDA and BDZ receptor bearing cells in AD neuropathology. AMPA receptor losses do not parallel the pathology, suggesting that AMPA receptors are not directly correlated with the pathology.