Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A...

Area of Science:

• Neuroscience
• Immunology
• Biomarker Discovery

Background:

• HIV-associated neurocognitive impairment (NCI) persists in people with HIV (PWH) despite antiretroviral therapy (ART).
• Chronic neuroinflammation, even with viral suppression, contributes to HIV-associated NCI pathogenesis.
• Growth Differentiation Factor 15 (GDF15) is implicated in inflammatory and metabolic stress responses and neurological conditions.

Purpose of the Study:

• To investigate the relationship between Growth Differentiation Factor 15 (GDF15) expression and HIV-associated neurocognitive impairment (NCI).
• To explore GDF15 as a potential biomarker for NCI in people with HIV (PWH).

Main Methods:

• Analysis of GDF15 levels in cerebrospinal fluid (CSF) and brain tissue from deceased PWH.
• Utilized immunoblotting, immunohistochemistry, double immunolabeling, and ELISA techniques.
• Categorized PWH into neurocognitively unimpaired (NUI) and HIV-associated NCI groups based on neuropsychological exams.

Main Results:

• GDF15 protein levels were significantly higher in the frontal cortices of PWH with NCI compared to NUI PWH.
• Higher plasma viral load observed in PWH with NCI (5.38 log10 copies/mL) versus NUI PWH (3.56 log10 copies/mL).

Conclusions:

• GDF15 may contribute to the pathogenesis of HIV-associated NCI, potentially via neuroinflammatory pathways.
• The strong correlation between GDF15 levels and cognitive impairment severity highlights its potential as an early detection and monitoring biomarker for NCI in PWH.