Publication Abstract Display | Type: Published Manuscript | Title: Neprilysin in the cerebrospinal fluid and serum of patients infected with HIV1- Subtypes C and B. | Authors: de Almeida S, Tang B, Ribeiro C, Rotta I, Vaida F, Piovesan M, Batistela Fernandes S, Letendre S, Potter M, Ellis RJ | Year: 2018 | Publication: Journal of Acquired Immune Deficiency Syndromes (1999) | Volume: 78 Issue: 2 Pages: 248-256 | Abstract:OBJECTIVE-:
Neprilysin (NEP) is the dominant Aβ peptide-degrading enzyme in the brain. HIV-1 subtype B Tat protein is known to interfere with NEP function, but whether this is true of HIV-1C Tat, which has a defective chemokine motif, is not known. This study aimed to analyze the impact of HIV subtype on NEP-mediated cleavage of Aβ by comparing CSF and serum levels of NEP between HIV+ (27 patients with HIV-1B and 26 with HIV-1C), healthy HIV- controls (n=13); and patients with Alzheimer's disease (AD,n=24).
METHODS-:
NEP, as well as Aβ oligomers 38, 40, 42 levels were measured in CSF and serum by Immunoassays. Ratios between NEP and Aβ-38,40,42, and total were calculated in CSF and serum. Comparisons between HIV(+) and HIV(-) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression.
RESULTS-:
Levels of NEP and ratios in CSF were comparable for HIV-1C and B subtypes. The ratio of serum NEP/Aβ-40 was lower for HIV1-C than HIV1-B (p=0.032). The CSF/serum index of NEP/Aβ-40, NEP/Aβ-42, and NEP/Aβ- total were lower for HIV1-B than HIV1-C (p=0.008, 0.005 and 0.017 respectively); corroborating the findings for serum. CSF NEP was comparable for HIV+, HIV-, and AD.
CONCLUSION-:
There was impact of HIV subtype on NEP. The ratio of NEP/Aβ-40 on serum was lower on HIV1-C than HIV1-B. These results are consistent with the results of CSF Aß-42 levels decreased in HIV1-C compared with HIV1-B; suggesting higher amyloid ß deposit on HIV1-C than HIV1-B. |
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