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J Acquir Immune Defic Syndr. 2018 Jun 1;78(2):248-256. doi: 10.1097/QAI.0000000000001666.

Neprilysin in the Cerebrospinal Fluid and Serum of Patients Infected With HIV1-Subtypes C and B.

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Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil.
Hospital Pequeno Principe, Curitiba, Paraná, Brazil.
HIV Neurobehavioral Research Program, University of California San Diego, CA.



Neprilysin (NEP) is the dominant Aβ peptide-degrading enzyme in the brain. HIV-1 subtype B transactivator of transcription protein is known to interfere with NEP function, but whether this is true of HIV-1C transactivator of transcription, 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 cerebrospinal fluid (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 disease (n = 24).


NEP and 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 sex and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression.


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.


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 Aβ-42 levels decreased in HIV1-C compared with HIV1-B, suggesting higher amyloid β deposit on HIV1-C than HIV1-B.

[Available on 2019-06-01]

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