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Journal of neuroimmunology
Published

Cerebrospinal fluid biomarkers associated with neurofilament light levels: A study in HIV disease

Authors

Enrico Ripamonti, Magnus Gisslén, Lars Hagberg, Pradeepthi Bathala, Shraddha Kale, Martin Stengelin, George Sigal, Jacob Wohlstadter, Henrik Zetterberg, Richard Price

Abstract

J Neuroimmunol. 2025 Jan 6;400:578521. doi: 10.1016/j.jneuroim.2025.578521. Online ahead of print.

ABSTRACT

BACKGROUND: A retrospective study was conducted in people with HIV (PWH) to explore potential cerebrospinal fluid (CSF) biomarkers linked to CSF neurofilament light levels (NfL), indicative of neuronal injury.

METHODS: A sample of 168 participants was tested, including 43 HIV-negative controls and PWH who were classified into subgroups based on HIV and treatment status. Twenty CSF protein biomarkers were analyzed for their association with CSF NfL concentrations using a linear regression forward selection strategy, adjusted for age and sex. Regression trees were utilized to visualize feature relationships.

RESULTS: Age-adjusted average concentrations of CSF NfL ranged from 427 pg/mL (SD = 190) in HIV- participants to 6456 pg/mL (SD = 46,024) in participants with HIV-associated dementia. Significant associations were found between specific biomarkers and CSF NfL levels in different participant subgroups. Noteworthy findings included correlations between CSF t-tau, CSF MCP-1, CSF TNF-α, and albumin ratio with CSF NfL levels in untreated PWH, and CSF IL-21 with CSF NfL in treated, virally suppressed PWH. Association between age and CSF NfL concentrations was a general finding.

CONCLUSION: We identified specific CSF biomarkers, including CSF t-tau protein, CSF MCP-1, and CSF TNF-α that associated with CSF NfL concentrations in untreated PWH and CSF IL-21 that associated with CSF NfL in PWH with effective treatment, shedding light on neuroinflammatory processes which may underlie HIV-related neuronal injury and the impact of antiviral therapy. Further investigations are needed to validate if elevated CSF IL-21 concentrations persist during long-term treatment, and if particular drug combinations are optimal for decreasing inflammatory latency.

PMID:39914269 | DOI:10.1016/j.jneuroim.2025.578521

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg