Objectives:  To determine if CSF levels of the apoptotic markers soluble Fas (sFas) and soluble Fas ligand (sFasL) are elevated in HIV-associated dementia (HIV-D) and if levels correlate with severity and course.

Background:  HIV-D develops in approximately 15% of AIDS patients.  The pathophysiology includes intense CNS macrophage activation and astrocytic and neuronal apoptosis. CSF sFas and sFasL are elevated in HIV-D, but these markers have not yet been related to dementia course.

Methods:  CSF and serum sFas and sFasL were measured by ELISA (Oncogene) in 16 patients with HIV-D and 30 HIV+ and 17 HIV- controls. Inflammatory and infectious conditions were excluded. All HIV+ patients were HAART naïve. sFas and sFasL levels were correlated with dementia severity and course (improvement, progression, or stability) using Memorial Sloan Kettering (MSK) scores. The median values for sFas and sFasL were compared between groups using the Mann-Whitney nonparametric test.

Results:  HIV-D patients had higher CSF sFas than HIV+ nondemented patients (p=0.020) and HIV- controls (p=0.004). Moderate to severely demented patients (MSK 2-3) had higher CSF sFas (p=0.014) than mildly demented patients (MSK 0.5-1). sFas levels trended higher in serum and CSF in progressive HIV-D.

Conclusion:  The astrocyte product sFas is elevated in CSF in HIV-D and correlates with dementia severity. Levels are higher in progressive dementia, corroborating observations with autopsy tissue. CSF sFas may be a useful marker for assessing severity and prognosis of HIV-D.

Figure 1:  Soluble Fas in the cerebrospinal fluid was significantly higher in patients with

HIV-D compared with HIV seronegative controls and HIV seropositive, nondemented controls.

Figure 2: Soluble Fas in the cerebrospinal fluid was significantly higher in patients with

moderate to severe dementia (MSK 2-3) compared with patients with mild dementia (MSK 0.5-1).