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

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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.

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Authors and Affiliations

  1. Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA

    Benjamin B. Gelman & Kimberly Schuenke

  2. Texas Center for NeuroAIDS Research, Department of Pathology, The University of Texas Medical Branch, 301 University Boulevard, 77555-0785, Galveston, TX, USA

    Benjamin B. Gelman

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Correspondence to Benjamin B. Gelman.

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This work was supported by the National Institutes of Health R24-MH59656, R24-NS45491, R01-DC04749, and R01-MH69200.

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Gelman, B.B., Schuenke, K. Brain aging in acquired immunodeficiency syndrome: Increased ubiquitin-protein conjugate is correlated with decreased synaptic protein but not amyloid plaque accumulation. Journal of NeuroVirology 10, 98–108 (2004). https://doi.org/10.1080/13550280490279816

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