Abnormal CSF Amyloid-beta 42 Levels Link HIV-Associated Cognitive Disease and Alzheimer's Disease.

Type: Published Abstract
Title: Abnormal CSF Amyloid-beta 42 Levels Link HIV-Associated Cognitive Disease and Alzheimer's Disease.
Authors: Clifford DB, Kauwe JSK, Teshome M, Shah AR, Spinner ML, Morris JC, Holtzman DM, Fagan AM
Year: 2008
Publication: 15th Conference on Retroviruses and Opportunistic Infections, Boston, Massachusetts, February 3-6, 2008
Volume: Issue: Pages:
Abstract:Background: To determine whether HIV-associated cognitive disorders shares common changes in biomarkers with Alzheimer’s disease (AD) (Brew et al., 2005), we examined amyloid beta-42 (beta-42 ) and tau levels in the cerebrospinal fluid (CSF) of nondemented individuals and those with early stage AD 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 beta-42 by commercial enzyme-linked immunosorbant assay (ELISA) (Innotest, Innogenetics, Ghent, Belgium), and Abeta40 by ELISA as described (Fagan et al., 2007). The sample included 67 HIV patients (18 HIV with normal cognition, 14 HAD, 35 MCMD, age range 28-63 years, mean 48), 50 non-demented individuals (age range 43-55 years, mean 50), and 71 individuals with very mild and mild DAT (age range 51-88 years, mean 74). CSF A-beta42 levels were compared between groups using ANCOVA after adjusting for age. Results: CSF A-beta42 levels were significantly lower than controls in DAT and cognitively impaired HIV patients (DAT p<0.0001; impaired HIV p<0.0001). CSF A-beta42 levels in non-impaired HIV subjects were not significantly different from controls (p=0.567). CSF A-beta40, total tau, and ptau181 in HIV were not different from controls, whereas both tau and ptau181 values were increased in DAT. Conclusions: Abnormal A-beta42 metabolism may occur in HIV disease during cognitive impairment but CSF tau levels distinguish HIV dementia from AD. Whether the decrease in A-beta42 in HIV-associated cognitive disease is associated with amyloid deposition as in AD or other causes remains to be determined.