Localization of ubiquitin in the plaques of five aged primates by dual-label fluorescent immunohistochemistry

J. B. Summers, M. A. Prendergast, W. D. Hill, J. J. Buccafusco

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Ubiquitin is involved in the cytosolic, ATP-dependent degradation of abnormal and short-lived proteins in all eukaryotic cells examined thus far. Studies of humans with neurological disorders, such as Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD), have identified ubiquitinated neurites surrounding plaques. Although the mechanism responsible for the accumulation of ubiquitinated products within dystrophic neurites is currently unknown, it has been suggested that protein turnover in these neurons may be altered by neurotoxic beta-amyloid (βA) in the surrounding neuropil. To investigate ubiquitin in the brains of non-human primates, dual-label immunohistochemistry was performed on sections from 15 monkeys (age range: 4-32 years) using anti-βA4 and anti-ubiquitin primary antibodies and fluorescent secondary antibodies. This paper reports finding ubiquitin colocalized with the majority (range: 55.7-100%) of plaques in five aged monkeys. Ubiquitin immunoreactivity (IR) appeared as granular structures with either the same orientation as plaques or localized in the periphery. These structures appear similar to the ubiquitinated neurites reported around the plaques in patients with AD and CJD. The plaque-containing monkeys also possessed varying degrees of vascular-associated βA IR, but only two possessed vascular lesions with granular ubiquitin IR in the surrounding neuropil. In addition, an apparent age-related accumulation of dot-like ubiquitinated material was observed in these 15 monkeys that was not associated with plaques. These results suggest that perturbations in ubiquitin-mediated protein turnover exist within some neurons of the aging monkey brain. Furthermore, similar mechanisms may be responsible for neuronal degeneration and the accumulation of ubiquitinated products within dystrophic neurites of both humans and monkeys.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalAlzheimer's Research
Volume3
Issue number1-2
StatePublished - Jan 1 1997

Keywords

  • Alzheimer's disease
  • Beta-amyloid
  • Immunohistochemistry
  • Plaques
  • Primates
  • Ubiquitin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology

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    Summers, J. B., Prendergast, M. A., Hill, W. D., & Buccafusco, J. J. (1997). Localization of ubiquitin in the plaques of five aged primates by dual-label fluorescent immunohistochemistry. Alzheimer's Research, 3(1-2), 11-21.