UC San Diego

Objective

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).

Methods

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.

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