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

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.

• Authors: Sérgio Monteiro de Almeida, Clea E Ribeiro, Indianara Rotta, Mauro Piovesan, Bin Tang, Florin Vaida, Sonia Mara Raboni, Scott Letendre, Michael Potter, Meire S Batistela Fernandes, Ronald J Ellis, HIV Neurobehavioral Research Center (HNRC) Group
• Journal: Journal of neurovirology (J Neurovirol) Vol. 24 Issue 1 Pg. 28-40 (02 2018) ISSN: 1538-2443 [Electronic] United States
• PMID: 29063514 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• APP protein, human
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Biomarkers
• MAPT protein, human
• tau Proteins

Topics

• Adult
• Aged
• Alzheimer Disease (blood, cerebrospinal fluid, immunology, pathology)
• Amyloid beta-Peptides (blood, cerebrospinal fluid)
• Amyloid beta-Protein Precursor (blood, cerebrospinal fluid)
• Biomarkers (blood, cerebrospinal fluid)
• Brain (metabolism, pathology)
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (immunology, virology)
• Cross-Sectional Studies
• Female
• Genotype
• HIV Infections (blood, cerebrospinal fluid, immunology, pathology)
• HIV-1 (classification, genetics)
• Humans
• Male
• Middle Aged
• Neurons (metabolism, pathology)
• Viral Load
• tau Proteins (blood, cerebrospinal fluid)