Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
Open accessAbstract
BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. METHODS: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. FINDINGS: Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4(+) T cells. INTERPRETATION: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.
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NfL is a structural protein that can be detected in the blood at elevated levels in a variety of neurological diseases.
“NfL is a structural protein that can be detected in the blood at elevated levels in a variety of neurological diseases (2–5).”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [5]
The Discussion describes NFL’s structural role in axons, and the Results report elevated plasma NFL in some groups with HIV-related CNS injury. The Discussion says elevations across several other neurological diseases have been shown in CSF; it presents plasma NFL’s usefulness in those settings as an extrapolation, not an established finding. (LLM, conf=0.87)
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- Authors
- Gisslén, M., Price, R. W., Andreasson, U., Norgren, N., Nilsson, S., Hagberg, L., Fuchs, D., Spudich, S., Blennow, K., & Zetterberg, H.
- Affiliations
- University of Gothenburg (SE)
- University of California, San Francisco (US)
- Chalmers University of Technology (SE)
- Innsbruck Medical University (AT)
- Yale University (US)
- National Hospital for Neurology and Neurosurgery (GB)
- Corresponding author
- Gisslén, Magnus
- ORCID
- Venue
- EBioMedicine
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 3
- Pages
- 135-140
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC4739412
- OpenAlex
- W2180292573
- Cited by
- 481
- References
- 2
- Citations by year
- 2026: 33 · 2025: 36 · 2024: 46 · 2023: 35 · 2022: 58 · 2021: 55 · 2020: 64 · 2019: 60 · 2018: 42 · 2017: 35 · 2016: 16 · 2015: 1
- FWCI
- 15.85
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-05-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- EBioMedicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Chalmers Publication Library (Chalmers University of Technology) (submittedVersion)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Royal Swedish Academy of Sciences
- VINNOVA (2014-03496)
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet (2013-2546, K2010-63P-21562-01-4, K2011-58P-20931-01-4, K2011-61X-20401-05-6, K2013-61X-14002-13-5)
- National Institutes of Health (P01MH094177, P30 AI027763, R01MH62701, R21MH096619, UL1 RR024131)
- Sahlgrenska Universitetssjukhuset (ALFGBG-139671, ALFGBG-430271, ALFGBG-441051)
- Torsten Söderbergs Stiftelse
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- neurofilament light chain, plasma biomarkers, cerebrospinal fluid, HIV-associated neurocognitive disorders, HIV-associated dementia, antiretroviral therapy, CD4 count, neurodegeneration
- MeSH terms
- Adult, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Biomarkers, HIV Infections, Neurofilament Proteins, CD4 Lymphocyte Count, Viral Load, Central Nervous System Viral Diseases, Antiretroviral Therapy, Highly Active
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