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J Neurovirol. 2018 Feb;24(1):28-40. doi: 10.1007/s13365-017-0591-3. Epub 2017 Oct 23.

Biomarkers of neuronal injury and amyloid metabolism in the cerebrospinal fluid of patients infected with HIV-1 subtypes B and C.

Author information

1
Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil. sergio.ma@ufpr.br.
2
Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.
3
Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.
4
Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil.
5
Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil.
6
Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil.
7
HNRC-University of California-San Diego, San Diego, CA, USA.

Abstract

Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aβ) 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 β (sAPPα, sAPPβ), Aβ oligomers 38, 40, 42, and Aβ-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 Aβ-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 Aβ-42 (p = 0.002) and higher CSF indexes: [Aß-42/(240 + 1.18 T-tau)], P-tau181/Aβ-42, T-tau/Aβ-42, P-tau181/T-tau, sAPPα/β (all p ≤ 0.01) than AD. Compared to HIV(-), HIV(+) had lower CSF Aβ-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.

KEYWORDS:

Amyloid metabolism; Biomarkers; CSF; Central nervous system; HIV; Neuronal injury; Subtype

PMID:
29063514
PMCID:
PMC5792298
[Available on 2019-02-01]
DOI:
10.1007/s13365-017-0591-3

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