RESUMEN
Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aß) metabolism, this study aimed to compare CSF neural injury biomarkers between 27 patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV-negative controls, and 24 patients with Alzheimer's disease (AD). Immunoassays were used to measure soluble amyloid precursor protein α and ß (sAPPα, sAPPß), Aß oligomers 38, 40, 42, and Aß-total; phosphorylated tau (P-tau181), and total tau (T-tau). Comparisons between HIV(+) and HIV(-) (including AD) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression. The p values were corrected for multiple testing with the Benjamini-Hochberg procedure. CSF Aß-42 and Hulstaert (P-tau181) index were lower in HIV1-C than B (p = 0.03, and 0.049 respectively); subtypes did not differ on other CSF biomarkers or ratios. Compared to AD, HIV(+) had lower CSF levels of T-tau, P-tau181 (p < 0.001), and sAPPα (p = 0.041); HIV(+) had higher CSF Aß-42 (p = 0.002) and higher CSF indexes: [Aß-42/(240 + 1.18 T-tau)], P-tau181/Aß-42, T-tau/Aß-42, P-tau181/T-tau, sAPPα/ß (all p ≤ 0.01) than AD. Compared to HIV(-), HIV(+) had lower CSF Aß-42, and T-tau (all p ≤ 0.004). As conclusion, amyloid metabolism was influenced by HIV infection in a subtype-dependent manner. Aß-42 levels were lower in HIV1-C than B, suggesting that there may be greater deposition of Aß-42 in HIV1-C. These findings are supported by CSF Hulstaert (P-tau181) index. Differences between HIV and AD in the patterns of Aß and Tau biomarkers suggest that CNS HIV infection and AD may not share some of same mechanisms of neuronal injury.
Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Precursor de Proteína beta-Amiloide/líquido cefalorraquídeo , Infecciones por VIH/líquido cefalorraquídeo , VIH-1/clasificación , Proteínas tau/líquido cefalorraquídeo , Adulto , Anciano , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/sangre , Precursor de Proteína beta-Amiloide/sangre , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Encéfalo/metabolismo , Encéfalo/patología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Estudios Transversales , Femenino , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/patología , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Neuronas/patología , Carga Viral , Proteínas tau/sangreRESUMEN
OBJECTIVE: Neprilysin (NEP) is the dominant Aß 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 Aß 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 Aß oligomers 38, 40, 42 levels were measured in CSF and serum by immunoassays. Ratios between NEP and Aß-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/Aß-40 was lower for HIV1-C than HIV1-B (P = 0.032). The CSF/serum index of NEP/Aß-40, NEP/Aß-42, and NEP/Aß-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/Aß-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.