Associative and predictive biomarkers of dementia in HIV-1-infected patients.
BACKGROUND
Infection with HIV can result in a debilitating CNS disorder known as HIV dementia (HIV-D). Since the advent of highly active antiretroviral therapy (HAART), the incidence of HIV-D has declined, but the prevalence continues to increase. In this new era of HIV-D, traditional biomarkers such as CSF viral load and monocyte chemotactic protein 1 levels are less likely to be associated with dementia in patients on HAART and biomarkers that can predict HIV-D have not yet been identified.


OBJECTIVE
To identify biomarkers that are associated with and can predict HIV-D.


METHODS
We grouped patients with HIV based on changes in cognitive status over a 1-year period and analyzed sphingolipid, sterol, triglyceride, antioxidant, and lipid peroxidation levels in CSF.


RESULTS
We found that increased levels of the vitamin E and triglyceride C52 predicted the onset or worsening of dementia. Elevated levels of sphingomyelin were associated with inactive dementia. Elevated levels of ceramide and the accumulation of 4-hydroxynonenals were associated with active dementia.


CONCLUSIONS
We interpret these findings to indicate that early in the pathogenesis of HIV dementia, there is an up-regulation of endogenous antioxidant defenses in brain. The failure of this attempted neuroprotective mechanism leads to the accumulation of sphingomyelin and moderate cognitive dysfunction. The breakdown of this enlarged pool of sphingomyelin to ceramide and the accumulation of highly reactive aldehydes are associated with declining cognitive function. Thus, elevations in endogenous protective mechanisms may identify patients who are at increased risk of the development of HIV dementia.
Bandaru
V V R
VV
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
McArthur
J C
JC
Sacktor
N
N
Cutler
R G
RG
Knapp
E L
EL
Mattson
M P
MP
Haughey
N J
NJ
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D000328:Adult; D000447:Aldehydes / Q000032:analysis / Q000134:cerebrospinal fluid; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D002518:Ceramides / Q000032:analysis / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D013107:Sphingolipids / Q000032:analysis / Q000134:cerebrospinal fluid; D013261:Sterols / Q000032:analysis / Q000134:cerebrospinal fluid; D014280:Triglycerides / Q000032:analysis / Q000134:cerebrospinal fluid; D015854:Up-Regulation; D014810:Vitamin E / Q000032:analysis / Q000134:cerebrospinal fluid
D000447:Aldehydes; D000975:Antioxidants; D015415:Biomarkers; D002518:Ceramides; D013107:Sphingolipids; D013261:Sterols; D014280:Triglycerides; D014810:Vitamin E; C027576:4-hydroxy-2-nonenal