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J Neurovirol. 2004 Apr;10(2):98-108.

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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Department of Pathology, The University of Texas Medical Branch, Galveston, Texas 77555-0785, USA.


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 (Abeta) fragment of the amyloid precursor protein (Abeta plaque) were both increased significantly in the hippocampal formation of older subjects. In subjects with AIDS, Ub-dots were increased whereas Abeta 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 (a-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.

[Indexed for MEDLINE]

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