Abstract:
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.
journal_name
Neurologyjournal_title
Neurologyauthors
Bandaru VV,McArthur JC,Sacktor N,Cutler RG,Knapp EL,Mattson MP,Haughey NJdoi
10.1212/01.wnl.0000260610.79853.47subject
Has Abstractpub_date
2007-05-01 00:00:00pages
1481-7issue
18eissn
0028-3878issn
1526-632Xpii
68/18/1481journal_volume
68pub_type
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