Background:  Aging is associated with increased risk for HIV-associated cognitive impairment. The pathophysiology of this impairment is not understood. To determine whether HIV-associated cognitive disorders shares common changes in biomarkers with Alzheimer’s disease, we examined amyloid b₄₂ (Ab₄₂) and tau levels in the cerebrospinal fluid (CSF) of nondemented individuals and those with early stage Alzheimer’s disease in comparison with individuals with HIV and HIV associated cognitive impairment.

Methods:  CSF samples collected from individuals with documented HIV and HIV-associated dementia (HAD) or HIV minor cognitive motor disorder (MCMD) were supplied by the Washington University CHARTER Study and the National NeuroAIDS Tissue Consortium (NNTC). CSF from nondemented individuals and those with very mild or mild dementia of the Alzheimer type (DAT) were obtained from the Washington University Alzheimer’s Disease Research Center. Diagnoses were derived in accordance with standard protocols that included detailed histories, neurological examinations, and psychometric testing; diagnoses were made prior to the results of the CSF assays. CSF was obtained and quickly frozen for later analysis. CSF samples were analyzed for total tau, phosphorylated tau₁₈₁ (ptau₁₈₁), and Ab₄₂ by commercial enzyme-linked immunosorbant assay (ELISA) (Innotest, Innogenetics, Ghent, Belgium), and Ab₄₀ by ELISA as described by Fagan et al. (2007). The sample included 67 HIV patients (18 HIV with normal cognition, 14 HAD, 35 MCMD, age range 28 to 63 years, mean 48), 50 non-demented individuals (age range 43 to 55 years, mean 50), and 71 individuals with very mild and mild DAT (age range 51 to 88 years, mean 74). CSF Ab₄₂ levels were compared between groups using ANCOVA after adjusting for age. 

Results:  CSF Ab₄₂ levels were significantly lower than controls in DAT and cognitively impaired HIV patients (DAT p <0.0001; impaired HIV p <0.0001). CSF Ab₄₂ levels in non-impaired HIV subjects were not significantly different from controls (p = 0.567). CSF Ab₄₀, total tau, and ptau₁₈₁ in HIV were not different from controls, whereas both tau and ptau₁₈₁ values were increased in DAT.

Conclusions:  Abnormal Ab₄₂ metabolism may occur in HIV disease during cognitive impairment but CSF tau levels distinguish HIV dementia from Alzheimer’s disease. Whether the decrease in Ab₄₂ in HIV-associated cognitive disease is associated with amyloid deposition as in Alzheimer’s disease or other causes remains to be determined.