CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease

Abstract

Background: HIV-associated neurologic disorders (HAND) continue to develop in many patients with HIV. CSF amyloid measurements in HAND have been reported to be similar to those in dementia of the Alzheimer type (DAT). Confirmatory evaluation of this finding in carefully evaluated subjects is needed.

Methods: CSF specimens were obtained from subjects clinically categorized with normal cognition from the general population, HIV+ subjects with normal cognition, HIV+ subjects with impaired cognition, or presumed HIV- subjects with mild DAT. CSF measurements of beta-amyloid((1-42)) (Abeta42), beta-amyloid((1-40)) (Abeta40), total tau (t-tau), and phosphorylated tau (p-tau181) were performed.

Results: CSF Abeta42 measured in 49 HAND subjects had a median level of 501 pg/mL, which was lower than that of 50 controls of similar age who had median of 686 pg/mL (p < 0.0001) or 21 HIV+ subjects without cognitive impairment who had median of 716 pg/mL (p < 0.003). HAND subjects had similar CSF Abeta42 to 68 subjects with mild DAT. There was no difference of CSF Abeta40 between the groups. Tau and p-tau181 was elevated in DAT, but slightly lower than control in both HIV+ groups.

Conclusions: beta-Amyloid((1-42)) (Abeta42) measurements in CSF of cognitively impaired patients with HIV are similar to those in patients with mild dementia of the Alzheimer type (DAT). Normal or slightly depressed CSF tau and p-tau181 measurements distinguish these patients with HIV-associated neurologic disorders (HAND) from patients with DAT. Further evaluation of amyloid metabolism in patients with HIV cognitive disorder is needed to understand the implications of depressed CSF Abeta42 in the setting of HAND.

Figure CSF biomarkers (A) Aβ42 levels in HIV-negative controls without dementia (controls), individuals with dementia of the Alzheimer type (DAT), HIV-positive individuals without dementia (HIV), and individuals with HIV-associated neurologic disorders (HAND). p Values of less than 0.05 from the least squares means difference matrix are shown. (B) Aβ40 levels in the 4 groups. There are no significant differences. (C) Tau levels in the 4 groups. DAT is significantly higher than all other groups. Both HIV and HAND are significantly lower than controls. No other significant associations. (D) p-tau181 levels in the 4 groups. DAT is significantly higher than controls, HIV, and HAND. The HAND group is significantly lower than controls. No other significant associations.