Alz-50 immunoreactive neuropil differentiates hippocampal complex subfields in Alzheimer's disease

Abstract

The topographic distribution of Alz-50 containing profiles was determined within the hippocampal formation and anterior parahippocampal gyrus by using a monoclonal antibody directed against the A68 protein in normal and Alzheimer's diseased (AD) brains. Although there was a paucity of immunoreactive neuropil in the normal hippocampal complex, there were a few Alz-50 positive neurons that occupied the hippocampal subfield, CA2. In most AD cases, Alz-50 immunoreactive neuropil was prominent in the outer two-thirds of the molecular layer of the dentate gyrus, although a few cases exhibited staining in the inner third of the molecular layer. CA2 was characterized by an increased density of neuropil staining within stratum pyramidale. The neuropil in subfield CA1 was stained densely with Alz-50 in strata oriens, pyramidale, and at the border between strata lacunosum-moleculare and radiatum. Alz-50 immunostained neurites occupied primarily the lateral two-thirds of the subiculum proper, whereas only sparse staining was seen in the adjacent presubiculum. Alz-50 neuropil and neuronal staining displayed three distinct laminar patterns along the mediolateral extent of the entorhinal cortex, whereas the perirhinal cortex exhibited a bilaminar pattern of immunoreactivity involving heavy staining in layers 1-3 as compared to layer 5. In general, the density of Alz-50 neurite staining in the neuropil appeared inversely proportional to the distribution of Alz-50 immunoreactivity within dendritic and somal compartments. Interestingly, the patterns of Alz-50 staining observed in the hippocampal complex in AD coincides with patterns of well-characterized afferent fiber pathways to these regions, thus further supporting the suggestion that hippocampal subfield specific pathology effectively disconnects medial temporal structures from adjacent neocortex in AD.