Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study
<b>Background/Objectives</b>: 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, even in th...
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2025-01-01
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| Online Access: | https://www.mdpi.com/2076-3425/15/1/49 |
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| author | Ali Boustani Mary K. Ford Jacqueline R. Kulbe Anna E. Laird Leeann Shu Matthew Spencer Bryant Avalos Kyle C. Walter Ronald J. Ellis Jerel Adam Fields |
| author_facet | Ali Boustani Mary K. Ford Jacqueline R. Kulbe Anna E. Laird Leeann Shu Matthew Spencer Bryant Avalos Kyle C. Walter Ronald J. Ellis Jerel Adam Fields |
| author_sort | Ali Boustani |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: 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, even in those with successful viral suppression. Growth Differentiation Factor 15 (GDF15), a protein involved in inflammatory and metabolic stress responses, has emerged as a key player and potential biomarker for various neurological conditions. This study investigates the relationship between GDF15 expression and HIV-associated NCI. <b>Methods</b>: PWH from the California NeuroAIDS Tissue Network (CNTN) underwent comprehensive neuropsychological exams within 12 months before death and were categorized based on cognitive performance. We examined GDF15 levels in their CSF (Cerebrospinal Fluid) and brain tissues using immunoblotting, immunohistochemistry, double immunolabeling, and ELISA. <b>Results</b>: The cohort was of a similar age across HIV-associated NCI statuses (mean = 40.5), with a predominance of males (77%). The mean plasma viral load was 3.56 log<sub>10</sub> copies/mL for Neurocognitively Unimpaired (NUI) PWH and 5.38 log10 copies/mL for people with HIV-associated NCI. GDF15 protein levels were significantly elevated in the frontal cortices of PWH with NCI compared to NUI PWH. <b>Conclusions</b>: The 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 the early detection and monitoring of NCI in PWH. |
| format | Article |
| id | doaj-art-075cf71bf8a840cda8506e5d204986ed |
| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj-art-075cf71bf8a840cda8506e5d204986ed2025-01-24T13:25:48ZengMDPI AGBrain Sciences2076-34252025-01-011514910.3390/brainsci15010049Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot StudyAli Boustani0Mary K. Ford1Jacqueline R. Kulbe2Anna E. Laird3Leeann Shu4Matthew Spencer5Bryant Avalos6Kyle C. Walter7Ronald J. Ellis8Jerel Adam Fields9Department of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USADepartment of Neurosciences, University of California San Diego, San Diego, CA 92093, USADepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USA<b>Background/Objectives</b>: 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, even in those with successful viral suppression. Growth Differentiation Factor 15 (GDF15), a protein involved in inflammatory and metabolic stress responses, has emerged as a key player and potential biomarker for various neurological conditions. This study investigates the relationship between GDF15 expression and HIV-associated NCI. <b>Methods</b>: PWH from the California NeuroAIDS Tissue Network (CNTN) underwent comprehensive neuropsychological exams within 12 months before death and were categorized based on cognitive performance. We examined GDF15 levels in their CSF (Cerebrospinal Fluid) and brain tissues using immunoblotting, immunohistochemistry, double immunolabeling, and ELISA. <b>Results</b>: The cohort was of a similar age across HIV-associated NCI statuses (mean = 40.5), with a predominance of males (77%). The mean plasma viral load was 3.56 log<sub>10</sub> copies/mL for Neurocognitively Unimpaired (NUI) PWH and 5.38 log10 copies/mL for people with HIV-associated NCI. GDF15 protein levels were significantly elevated in the frontal cortices of PWH with NCI compared to NUI PWH. <b>Conclusions</b>: The 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 the early detection and monitoring of NCI in PWH.https://www.mdpi.com/2076-3425/15/1/49GDF15HIV-associated NCIneuroinflammation |
| spellingShingle | Ali Boustani Mary K. Ford Jacqueline R. Kulbe Anna E. Laird Leeann Shu Matthew Spencer Bryant Avalos Kyle C. Walter Ronald J. Ellis Jerel Adam Fields Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study Brain Sciences GDF15 HIV-associated NCI neuroinflammation |
| title | Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study |
| title_full | Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study |
| title_fullStr | Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study |
| title_full_unstemmed | Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study |
| title_short | Increased Growth Differentiation Factor 15 Levels Are Associated with HIV-Associated Neurocognitive Impairment: A Pilot Study |
| title_sort | increased growth differentiation factor 15 levels are associated with hiv associated neurocognitive impairment a pilot study |
| topic | GDF15 HIV-associated NCI neuroinflammation |
| url | https://www.mdpi.com/2076-3425/15/1/49 |
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