Potential role for white matter lysosome expansion in HIV-associated dementia

Benjamin Gelman, Vicki M. Soukup, Charles E. Holzer, Roderic H. Fabian, Kimberly W. Schuenke, Michael J. Keherly, Frances J. Richey, Christopher J. Lahart

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Expansion of the lysosomal apparatus occurs in subcortical white matter in brains from persons with AIDS. This study examined whether HIV-associated subcortical dementia (HAD) is significantly related to this lysosomal anomaly. Brain cortex and adjacent white matter from the middle frontal gyrus were obtained from the National NeuroAIDS Tissue Consortium. Lysosomal hydrolase activity was assayed in 57 subjects who underwent neuropsychological testing within 6 months prior to autopsy. Decedents were evaluated from 4 geographical sites in the United States: Galveston/Houston, Texas (n = 36), Los Angeles, California (n = 5), New York, New York (n = 5), and San Diego, California (n = 11). Increased β-glucuronidase activity, a representative lysosomal glycosidase, was correlated with the amount of neurocognitive impairment. Significant correlation was present in 5 of 7 functional testing domains, including some that draw upon frontal lobe output (r = 0.419; P < 0.002). The biochemical anomaly was negligible in cerebral cortex and cerebrospinal fluid and was not correlated with brain dysfunction in those compartments. Glycosidase activation was associated significantly with increased HIV RNA concentration in brain tissue (r = 0.469; P < 0.021) and possibly with HIV RNA in cerebrospinal fluid (r = 0.266; P < 0.067). HIV RNA in blood plasma was not correlated. These results support the suggestion that abnormal metabolism in white matter glial cells contributes to cognitive slowing in persons with HAD. Because membrane turnover is routed through the endosome-lysosome apparatus, these data are in agreement with brain spectroscopic data that have suggested that there is an increase in membrane turnover in white matter glia.

Original languageEnglish (US)
Pages (from-to)422-425
Number of pages4
JournalJournal of Acquired Immune Deficiency Syndromes
Volume39
Issue number4
DOIs
StatePublished - Aug 1 2005

Fingerprint

AIDS Dementia Complex
Lysosomes
HIV
Brain
Glycoside Hydrolases
RNA
Neuroglia
Cerebrospinal Fluid
Dementia
Membranes
Los Angeles
Endosomes
Glucuronidase
Frontal Lobe
Hydrolases
Cerebral Cortex
Autopsy
Acquired Immunodeficiency Syndrome
White Matter

Keywords

  • Aids
  • Dementia
  • HIV encephalitis
  • Lysosome
  • Myelin
  • White matter

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Gelman, B., Soukup, V. M., Holzer, C. E., Fabian, R. H., Schuenke, K. W., Keherly, M. J., ... Lahart, C. J. (2005). Potential role for white matter lysosome expansion in HIV-associated dementia. Journal of Acquired Immune Deficiency Syndromes, 39(4), 422-425. https://doi.org/10.1097/01.qai.0000164250.41475.f2

Potential role for white matter lysosome expansion in HIV-associated dementia. / Gelman, Benjamin; Soukup, Vicki M.; Holzer, Charles E.; Fabian, Roderic H.; Schuenke, Kimberly W.; Keherly, Michael J.; Richey, Frances J.; Lahart, Christopher J.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 39, No. 4, 01.08.2005, p. 422-425.

Research output: Contribution to journalArticle

Gelman, B, Soukup, VM, Holzer, CE, Fabian, RH, Schuenke, KW, Keherly, MJ, Richey, FJ & Lahart, CJ 2005, 'Potential role for white matter lysosome expansion in HIV-associated dementia', Journal of Acquired Immune Deficiency Syndromes, vol. 39, no. 4, pp. 422-425. https://doi.org/10.1097/01.qai.0000164250.41475.f2
Gelman, Benjamin ; Soukup, Vicki M. ; Holzer, Charles E. ; Fabian, Roderic H. ; Schuenke, Kimberly W. ; Keherly, Michael J. ; Richey, Frances J. ; Lahart, Christopher J. / Potential role for white matter lysosome expansion in HIV-associated dementia. In: Journal of Acquired Immune Deficiency Syndromes. 2005 ; Vol. 39, No. 4. pp. 422-425.
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