Three-dimensional structures of canine senile plaques

In this study, the three-dimensional structures of two types of canine senile plaques (SP), diffuse plaques (DP) and mature plaques (MP), were compared using a confocal laser scanning microscope. The three-dimensional observation revealed that canine DP were uneven nebula-like assemblies of amyloid-β (Aβ), while MP were comparatively uniform assemblies of membrane-like or fibrous Aβ materials with some differences among subtypes (primitive, classic and compact). We also noticed the presence of areas with low-density Aβ deposition inside DP and MP, indicating degradation of Aβ. Double staining for Aβ and other SP constituents was also conducted. Amyloid precursor protein (APP) was mainly deposited as rough granules around Aβ assemblies in DP and both inside and around Aβ assemblies in MP. The pattern of ubiquitin deposition was quite similar to that of APP. Glial fibrillary acidic protein-positive astroglial projections were found around and inside Aβ assemblies in both types of SP, but were more prominent in MP than DP. DP were often invaded by neurofilament-positive neuronal processes (neurites), while no such neurites were observed inside MP. Dystrophic neurites were, however, frequently detected around MP. These results clearly showed that canine DP and MP have completely different three-dimensional structures, consistent with different processes of DP and MP formation.