Ultrastructure of neurofibrillary tangles in the cerebral cortex of sheep.

Recently, we reported that neurofibrillary tangles (NFTs) of the Alzheimer type develop in the cerebral cortex of aged sheep (Ovis aries). In the current study, we utilized light and electron microscopic immunocytochemistry to describe in greater detail the characteristics of sheep NFTs during early stages of neurofibrillary degeneration. We investigated neurons that were stained using the monoclonal antibody Alz-50 and that contained relatively small numbers of paired helical filaments (PHFs). Serially cut ultrathin sections were evaluated to take maximal advantage of ultrastructural resolution. At the light microscope level, we observed preferential localization of Alz-50 immunoreactive accumulations at dendritic branch points in early NFTs. A similar staining pattern was observed using the monoclonal antibody AT8 which recognizes a phosphorylated epitope on tau. Ultrastructurally, we found that Alz-50 staining at dendritic branch points was associated with clusters of ribosomes. The focal deposition of phosphorylated tau proteins at dendritic branch points may indicate a link between the initial stages of neurofibrillary pathology and specific cytoskeletal alterations that involve dendritic remodeling. Neurons that contained relatively small numbers of PHFs appeared otherwise healthy with regard to their cytoskeleton and organelles.