Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls

Abstract

Several CSF biomarkers of neuronal injury have been studied in people living with HIV. At this time, the most useful is the light subunit of the neurofilament protein (NFL). This major structural component of myelinated axons is essential to maintain axonal caliber and to facilitate effective nerve conduction. CSF concentrations of NFL provide a sensitive marker of CNS injury in a number of neurological diseases, including HIV-related neuronal injury.Areas Covered: In this review, the authors describe CSF NFL concentrations across the spectrum of HIV-infection, from its early acute phase to severe immunosuppression, with and without neurological conditions, and with and without antiretroviral treatment (n = 516). Furthermore, in order to provide more precise estimates of age-related upper limits of CSF NFL concentrations, the authors present data from a large number (n = 359) of HIV-negative controls. Expert Commentary: Recently a new ultrasensitive diagnostic assay for quantification of NFL in plasma has been developed, providing a convenient way to assess neuronal damage without having to perform a lumbar puncture. This review also considers our current knowledge of plasma NFL in HIV CNS infection.

Neurofilament light chain in blood is negatively associated with neuropsychological performance in HIV-infected adults and declines with initiation of antiretroviral therapy

“…In contrast, there was a trend towards longitudinal increase in plasma NFL in the group of HIVnegative participants, though this was not statistically significant. A relationship between increasing age and increasing NFL has been found in other studies (Jessen Krut et al, 2014; Yilmaz et al, 2017), and therefore may reflect neuronal damage over time. Plasma NFL concentrations also correlated closely with CSF NFL concentrations, confirming the findings of a recent study (Gisslen et al, 2016) and supporting the conclusion that plasma NFL reflects neuronal injury in the CNS during HIV.…”

Diagnostic value of plasma neurofilament light: A multicentre validation study

“…However, even under normal circumstances, low levels of NfL are continuously released from axons in an age-dependent manner with typical NfL reference ranges in the CSF increasing by 2.5-fold between ages 20-50 years and doubling by the age of 70 8,9 . A considerable drawback of CSF NfL, and all CSF biomarkers, is the perceived invasiveness or complexity attached to lumbar punctures which will undoubtedly limit use for routine clinical assessment.…”

Cerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders

“…It is mainly produced by activated macrophages/monocytes, and its CSF levels increase with increasing immunosuppression in untreated HIV-infected individuals and are highest in patients with HAD and CNS opportunistic infections [24, 25]. CSF neurofilament light protein (NFL) is a sensitive marker of HIV-induced axonal injury [25, 26, 27•]. CSF NFL concentrations are highest in individuals with HAD where neuronal damage and loss are prominent, but some untreated individuals without neurocognitive symptoms with low CD4 + T cell counts may also have high levels.…”

“…CSF NFL was measured using a commercially available sandwich ELISA (NF-light® ELISA kit, UmanDiagnostics AB, Umeå, Sweden). Upper reference values are age-dependent [27•]. CSF neopterin was analyzed using a commercially available immunoassay (BRAHMS, Berlin, Germany) with an upper normal reference value of 5.8 nmol/L [24].…”