Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study

• Plasma NFL is a sensitive marker of neuronal injury
• Plasma and CSF NFL concentrations were highly correlated
• Plasma NFL is useful to detect active axonal injury in treated and untreated HIVA sensitive blood biomarker of neuronal injury has long been sought for. Here we describe an ultrasensitive quantification measurement of the axonal neurofilament light chain protein (NFL) in blood. We test this in the setting of HIV brain injury in which cerebrospinal fluid (CSF) NFL has been well characterized and noted to be a reliable biomarker of neuronal injury.Blood and CSF NFL were highly correlated and measurement of plasma NFL was able to detect both severe and subclinical neuronal injury in HIV.CSF NFL is elevated in a wide range of additional neurodegenerative settings, so the reported findings likely have broader implications, though this requires additional direct study.

BackgroundCerebrospinal 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.MethodsTo 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.FindingsPlasma 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.InterpretationThese 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.