Abstract Details

Title Increased Levels of GDF15 Protein in the Brain are Associated with Neurocognitive Dysfunction in People with HIV

Topic Infectious Disease

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 10-002

Objective

To investigate the relationship between GDF15 expression and HIV-associated NCI

Background HIV-associated neurocognitive impairment (NCI) remains a prevalent issue among people with HIV (PWH) despite advancements in antiretroviral therapy (ART). The pathogenesis of HIV-associated NCI is linked to chronic neuroinflammation caused by HIV and ART, which can lead to neuronal damage and neurodegeneration. Growth Differentiation Factor 15 (GDF15), a protein involved in inflammatory and metabolic stress responses, has emerged as a potential biomarker for various neurological conditions. Cannabidiol (CBD) is linked to anti-inflammation in cell culture and animal models. This study investigates the relationship between GDF15 expression and HIV-associated NCI.

Design/Methods We investigated its relationship with HIV-associated NCI in 22 PWH from the CNTN. Subjects underwent comprehensive neuropsychological exams within 12 months before death and were categorized based on cognitive performance. We examined GDF15 expression in brain tissues using immunoblotting, immunohistochemistry, and double immunolabeling and conducted in vitro experiments with brain cell models exposed to HIV-relevant stimuli.

Results The cohort was of similar age across HIV-associated NCI statuses (Mean=40.5), with a predominance of males (77%). The mean plasma viral load was 3627.3 copies/ml for cognitively normal PWH and 238200 copies/ml for people with HIV-associated NCI. GDF15 protein levels were significantly elevated in the frontal cortices of PWH with NCI compared to those without NCI. Increased GDF15 expression was observed in both gray and white matter, particularly in microglia, neurons, and astrocytes. In vitro experiments revealed that CBD, interleukin-1 beta, and ART modulated GDF15 expression.

Conclusions Findings indicate that GDF15 may play a role in the pathogenesis of HIV-associated NCI, possibly through neuroinflammatory mechanisms. The strong association between GDF15 levels and cognitive impairment severity suggests its potential as a biomarker for early detection and monitoring of NCI in PWH. Additionally, the modulatory effects of cannabidiol on GDF15 expression warrant further investigation as potential intervention strategy.

Authors/Disclosures
Ali Boustani, MD PRESENTER	Dr. Boustani has nothing to disclose.
Mary K. Ford	Miss Ford has nothing to disclose.
Jacqueline R. Kulbe, MD, PhD	Dr. Kulbe has nothing to disclose.
Anna Laird	Ms. Laird has nothing to disclose.
Leeann V. Shu	Miss Shu has nothing to disclose.
Matthew Spencer	Mr. Spencer has nothing to disclose.
Ronald J. Ellis, MD, PhD, FAAN (UC San Diego)	Dr. Ellis has nothing to disclose.
Jerel A. Fields, PhD	Dr. Fields has received intellectual property interests from a discovery or technology relating to health care.

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