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.