Alz-50 immunohistochemistry in the normal sheep striatum: a light and electron microscope study

Peter T. Nelson, Linda Marton, Clifford B. Saper

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Alz-50 is a monoclonal antibody raised against ventral forebrain tissue from patients with Alzheimer's disease (AD). It was originally believed that the antigen recognized by Alz-50 was only found in degenerating neurons. However, recent studies indicate that Alz-50 stains neurons in a limited but specific distribution in normal brains throughout life. As the antigen recognized by Alz-50 in normal brains may give some insight into the AD degenerative process, we characterized Alz-50 staining in the normal ovine striatum using immunoblots and immunocytochemistry at the light and electron microscope levels. We then compared the Alz-50 staining pattern with those of NADPH diaphorase histochemistry and immunocytochemistry using antisera against several neuropeptides. Alzheimer-related proteins, and heat-shock proteins. Western blot analysis indicated that the epitope recognized by Alz-50 in the normal sheep brain is on the microtubule-associated protein tau, and preadsorbing Alz-50 with a peptide corresponding to the amino terminus of the tau molecule eliminated staining. Alz-50 labeled a single population of cells in the ovine striatum, the medium aspiny neurons. At the light microscope level, the granular staining pattern closely resembled Alz-50 immunoreactive neurons in the normal human striatum and in cells undergoing early degeneration in AD. Alz-50 immunoreactive neurons stained immunocytochemically with antisera against somatostatin, neuropeptide Y, and histochemically for NADPH diaphorase. These cells were morphologically characterized by smooth dendrites, elaborate local axonal plexuses, and indented nuclei with filamentous inclusions. Ultrastructurally, Alz-50 immunodecorated ribosomes and membranous structures (e.g. vesicles, endoplasmic reticulum), and many boutons which contained Alz-50-positive synaptic vesicles. None of the antisera against other Alzheimer-related proteins, including paired helical filament protein, ubiquitin, β-amyloid protein, or heat-shock proteins specifically stained the population of cells labelled by Alz-50. Other tau antisera also did not specifically stain these cells. We conclude that Alz-50 recognizes an amino terminal epitope that is exposed on tau proteins within a single, discrete population of neurons in the normal sheep striatum. The presence of this epitope in a normal cell population raises the possibility that the early stages of AD degeneration may involve the activation of a normal cellular pathway that modifies the tau molecule.

Original languageEnglish
Pages (from-to)285-297
Number of pages13
JournalBrain Research
Volume600
Issue number2
DOIs
StatePublished - Jan 15 1993

Bibliographical note

Funding Information:
Acknowledgements. We thank Dr. Karl Stefannson for valuable counsel, Quan Hue Ha, Christopher Hazuka, and Steven Price lor technical assistance, Dr. Dennis Selkoe for his contribution of the antibody '1280', Dr. Peter Davies for the antibodies Alz-5(I and PHF-1, and Dr. William Welch for antibodies N27 and C92, as well as polyclonal anti-hsp 28. This work was supported by USPHS grants AG1)9466 and HD1)1)7(19, and by the Brain Research Foundation and William D. Mabie Research Fund.

Keywords

  • Alz-50
  • Heat-shock protein
  • Immunohistochemistry
  • NADPH diaphorase
  • Striatum
  • Tau protein

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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