ULTRASTRUCTURE OF NEUROFIBRILLARY TANGLES IN THE CEREBRAL-CORTEX OF SHEEP

Recently, we reported that neurofibrillary tangles (NFTs) of the Alzhe imer type develop in the cerebral cortex of aged sheep (Ovis aries). I n the current study, we utilized light and electron microscopic immuno cytochemistry to describe in greater detail the characteristics of she ep NFTs during early stages of neurofibrillary degeneration. We invest igated neurons that were stained using the monoclonal antibody Alz-50 and that contained relatively small numbers of paired helical filament s (PHFs). Serially cut ultrathin sections were evaluated to take maxim al advantage of ultrastructural resolution. At the light microscope le vel, we observed preferential localization of Alz-50 immunoreactive ac cumulations at dendritic branch points in early NFTs. A similar staini ng pattern was observed using the monoclonal antibody AT8 which recogn izes a phosphorylated epitope on tau. Ultrastructurally, we found that Alz-50 staining at dendritic branch points was associated with cluste rs of ribosomes. The focal deposition of phosphorylated tau proteins a t dendritic branch points may indicate a link between the initial stag es of neurofibrillary pathology and specific cytoskeletal alterations that involve dendritic remodeling. Neurons that contained relatively s mall numbers of PHFs appeared otherwise healthy with regard to their c ytoskeleton and organelles.