Ultrastructure of neurofibrillary tangles in the cerebral cortex of sheep

P. T. Nelson, C. B. Saper

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageEnglish
Pages (from-to)315-323
Number of pages9
JournalNeurobiology of Aging
Issue number3
StatePublished - 1995

Bibliographical note

Funding Information:
We thank Quan Hue Ha and William Appel for excellent technical work and Peter Davies for providing the Alz-50 antibody. This work was supported in part by grants from the Mathers Foundation and the Fidelity Foundation and USPHS Grant AG12856.


  • AT8
  • Alz-50
  • Alzheimer's disease
  • Brain
  • Electron microscopy
  • Immunocytochemistry
  • Neurofibrillary tangle
  • Sheep

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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