THE LOSS OF GLUR2(3) IMMUNOREACTIVITY PRECEDES NEUROFIBRILLARY TANGLEFORMATION IN THE ENTORHINAL CORTEX AND HIPPOCAMPUS OF ALZHEIMER BRAINS

Double-immunolabeling techniques were employed to examine the distribu tion of GluR2(3) subunits and markers of early cytoskeletal changes (m ab MC1) within the entorhinal cortex (EC) and hippocampus of cases wit h varying degrees of Alzheimer disease (AD) pathology (stages I-VI by Braak and Braak). In addition, near-adjacent tissue sections were doub le-immunolabeled using antibodies against GluR2(3) and a marker of nor mal neuronal cytoskeleton (MAP2). In those cases classified as stages I-II, most layer II neurons of the EC and pyramidal neurons in the CA1 /subiculum were double-labeled with GluR2(3) and MAP2. An occasional M C1-labeled cell was observed, yet in no instance were these neurons do uble-labeled with GluR2(3). In cases with moderate AD pathology (stage s III-IV), layer II of the EC and CA1/subiculum were characterized by a substantial loss of GluR2(3)-labeled neurons, while many were still immunoreactive to MAP2. Notably, the loss of GluR2(3) immunolabeling w as accompanied by an increasing number of MC1-positive neurons. In no instance were GluR2(3) and MC1 co-localized within the same neuron. In cases with severe AD pathology (stages V-VI), the EC and CA1/subiculu m were almost completely devoid of GluR2(3)-positive neurons. MAP2-lab eled neurons also were reduced in number. In contrast, both regions co ntained an abundance of MC1-positive cells. That GluR2(3) and MC1 are not observed in the same neuron, together with the observation that th e number of GluR2(3)-labeled neurons decreases as the number of MC1-po sitive cells increases, suggest that a loss of GluR2(3) immunolabeling precedes the appearance of MC1 immunolabeling.