Cerebrospinal fluid proteomic profiling of HIV-1-infected patients with cognitive impairment.
Advanced HIV-1 infection is commonly associated with progressive immune suppression and the development of cognitive, motor, and behavior disturbances. In its most severe form, it is diagnosed as HIV-1 associated dementia (HAD) and can progress to profound functional disability and death. Despite prodigious efforts to uncover biomarkers of HAD, none can adequately reflect disease onset or progression. Thus, we developed a proteomics platform for HAD biomarker discovery and used it to perform a pilot study on cerebrospinal fluid (CSF) from HIV-1-infected people with or without HAD. A 2-dimensional electrophoresis (2-DE) map of a HAD CSF proteome was focused on differentially expressed proteins. 2-DE difference gel electrophoresis (2-D DIGE) analysis showed >90 differences in protein spots of which 20 proteins were identified. Differential expression of 6 proteins was validated by Western blot tests and included vitamin D binding protein, clusterin, gelsolin, complement C3, procollagen C-endopeptidase enhancer 1, and cystatin C. We posit that these proteins, alone or together, are potential HAD biomarkers.
Rozek
Wojciech
W
Center for Neurovirology and Neurodegenerative Disorders, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5800, USA.
Ricardo-Dukelow
Mary
M
Holloway
Sondra
S
Gendelman
Howard E
HE
Wojna
Valerie
V
Melendez
Loyda M
LM
Ciborowski
Pawel
P
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002555:Cerebrospinal Fluid / Q000378:metabolism* / Q000821:virology*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid*; D003176:Complement C3 / Q000737:chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005456:Fluorescent Dyes / Q000494:pharmacology; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000134:cerebrospinal fluid*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods*
D003176:Complement C3; D005456:Fluorescent Dyes