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Original Articles
The urokinase receptor is overexpressed in the AIDs dementia complex and other neurological manifestations
Article first published online: 25 MAR 2004
DOI: 10.1002/ana.20076
Copyright © 2003 American Neurological Association
1531-8249/asset/cover.gif?v=1&s=685ec69724c5ed4c8847ce939e70ceb45065856f "Annals of Neurology")
Additional Information
How to Cite
Cinque, P., Nebuloni, M., Santovito, M. L., Price, R. W., Gisslen, M., Hagberg, L., Bestetti, A., Vago, G., Lazzarin, A., Blasi, F. and Sidenius, N. (2004), The urokinase receptor is overexpressed in the AIDs dementia complex and other neurological manifestations. Ann Neurol., 55: 687–694. doi: 10.1002/ana.20076
Publication History
- Issue published online: 21 APR 2004
- Article first published online: 25 MAR 2004
- Manuscript Accepted: 24 JAN 2004
- Manuscript Revised: 23 JAN 2004
- Manuscript Received: 3 AUG 2003
Funded by
- Superior Institute of Health (Istituto Superiore di Sanità, Italy). Grant Number: 30.D.18
- European Union. Grant Numbers: FP5 QLG1 CT 2000 01131, FP6 contract no. 503297
- NIH (National Institute for Neurological Diseases and Stroke). Grant Numbers: R01 NS37660, R01 NS43103
- National Institute of Mental Health. Grant Number: R01 MH62701
- National Center for Research Resources. Grant Number: M01 RR00083
- Spanish AIDS (Sida) Project, Fundaciò la Marathò de TV3
- Abstract
- Article
- References
- Cited By
Abstract
The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in extracellular matrix degradation and cell migration in the central nervous system (CNS). To investigate the role of the uPA/uPAR system in the pathophysiology of acquired immunodeficiency syndrome dementia complex (ADC), we measured soluble uPAR (suPAR) levels in cerebrospinal fluid (CSF) and plasma from human immunodeficiency virus (HIV)-1–infected patients and controls. CSF suPAR levels were significantly higher in HIV-1–infected patients than in controls and in patients with ADC or opportunistic CNS infections (CNS-OIs) than in neurologically asymptomatic patients, irrespective of HIV-1 disease stage. The highest levels of suPAR were found in patients with ADC, and among those with CNS-OIs in patients with cytomegalovirus encephalitis or cryptococcosis. Plasma suPAR levels were higher in HIV-1–infected patients than in controls and increased with HIV-1 disease stage regardless of the presence of CNS disease. In patients with ADC or CNS-OIs, CSF suPAR levels correlated with CSF HIV-1 RNA, but not with plasma suPAR concentrations. Highly active antiretroviral therapy was associated with a significant and parallel decrease of both CSF suPAR and HIV-1 RNA. In brain tissue from patients with HIV-1 encephalitis, uPAR was highly expressed by microglial and multinucleated giant cells staining positively for HIV-1. The overexpression of uPAR in the CNS of patients with ADC suggests that the uPA/uPAR system may contribute to the tissue injury and neuronal damage in this disease. Ann Neurol 2004