Diffuse plaques associated with astroglial amyloid β protein, possibly showing a disappearing stage of senile plaques

Abstract

To clarify whether senile plaques disappear, we examined amyloid beta protein (A beta) deposits in non-demented subjects, and found novel diffuse plaques associated with astroglial A beta. Formalin-fixed paraffin-embedded sections from cortical areas were immunolabeled with a panel of A beta antibodies, and astroglial and microglial markers. Cerebral A beta deposition was primarily found as diffuse plaques (DP) in these subjects. A subset of DP was associated with clusters of intensely A beta-positive small granules. The clusters, which were located just adjacent to astroglial nucleus, had the characteristics of lipofuscin granules and, therefore, were quite different from "small stellate deposits". Substantial amounts of A beta-positive granules were found inside astrocytes by dual labeling of A beta and glial fibrillary acid protein, and the majority of astroglial A beta immunoreactivity was located on lipofuscin granules. A beta-positive granules lacked immunoreactivity with antisera for the N-terminal region of A beta. These peculiar DP showed a much weaker staining than ordinary DP. The DP associated with astroglial A beta were found in about one third of the subjects, although the density varied widely among individuals. From these findings, we propose that DP, which are associated with the N-terminal truncated A beta in astrocytes, represent the disappearing stage of senile plaques.