Brain aging in acquired immunodeficiency syndrome: Increased ubiquitin-protein conjugate is correlated with decreased synaptic protein but not amyloid plaque accumulation

Benjamin B. Gelman, Kimberly Schuenke

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Two neuropathological changes that are linked with biological and pathological aging were examined in subjects with end-stage acquired immunodeficiency syndrome (AIDS). Autopsy brain specimens were examined from 25 people who died from complications of AIDS and 25 comparison subjects who were human immunodeficiency virus (HIV)-negative, matched for age, gender, ethnicity, and postmortem time interval. These adults were stratified into three age groups: elderly (62 to 75 years), intermediate (55 to 60 years), and young (21 to 42 years). Ubiquitin-stained dotlike deposits (Ub-dots) and diffuse extracellular plaques containing the beta-amyloid (Aβ) fragment of the amyloid precursor protein (Aβ plaque) were both increased significantly in the hippocampal formation of older subjects. In subjects with AIDS, Ub-dots were increased whereas Aβ plaque counts were not significantly different. Western blotting confirmed that high-molecular-weight ubiquitin-protein conjugates (HMW-Ub-conj) were increased in AIDS. The band intensity of one HMW-Ub-conj species with an approximate molecular mass of 145 kDa was correlated significantly with increased acute phase inflammatory protein (α-1-antichymotrypsin) and decreased synaptophysin and growth-associated protein-43 band intensities. These results raise the possibility that HIV-related brain inflammation disturbs neuronal protein turnover through the ubiquitin-proteasome apparatus, and might increase the prevalence of age-associated neurodegenerative diseases by decreasing synaptic protein turnover through the proteasome.

Original languageEnglish (US)
Pages (from-to)98-108
Number of pages11
JournalJournal of neurovirology
Volume10
Issue number2
DOIs
StatePublished - Apr 2004

Keywords

  • Amyloid precursor protein
  • Autopsy
  • Diffuse plaque
  • Growth associated protein-43
  • HIV encephalitis
  • Proteasome
  • Synaptophysin
  • Ubiquitin
  • Western blotting

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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