SIMILARITIES IN THE AGE-RELATED HIPPOCAMPAL DEPOSITION OF PERIODIC ACID-SCHIFF-POSITIVE GRANULES IN THE SENESCENCE-ACCELERATED MOUSE P8 ANDC57BL 6 MOUSE STRAINS/

With advancing age, clusters of abnormal granules positive for periodi c acid-Schiff appear in the hippocampus bf C57BL/6 (B6) mice and the s enescence-accelerated mouse (SAM) P8. The granules can also be visuali zed with a polyclonal antibody to a 110,000 mol. wt laminin-binding pr otein and stain specifically with a monoclonal antibody to heparan sul fate proteoglycan. The present study used light- and electron-microsco pic analysis to compare the staining and morphological properties of t hese granules in SAM P8 hippocampus with those in B6 hippocampus at di fferent ages. The results of the light-microscopic analysis revealed t hat granules in SAM P8 and B6 had similar morphology, staining charact eristics and distribution patterns, and appeared to have a close assoc iation with astrocytic processes. The onset of granules in SAM P8 mice (at two to three months of age) was earlier than that observed in B6 mice (al four to six months of age), but the maximum incidence was sim ilar in both strains. Electron-microscopic analysis revealed that the granules in SAM P8 and B6 mice also had a very similar ultrastructure. Granules in both strains were surrounded by a discontinuous membrane and contained mostly crystalline-like, degenerated material. The succe ssive ultrastructural changes from the exterior to interior of the gra nules suggest that the degenerative process was initiated outside the granules and that degenerative structures migrate inward. Astrocytes a nd heparan sulfate proteoglycan are closely associated with beta-amylo id deposits in Alzheimer's disease. The presence of astrocyte-associat ed heparan sulfate proteoglycan-positive material in aged SAM P8 and B 6 mice might model age-related alterations in glia function possibly i nvolved in human cerebral amyloidogenesis.