Neurofilament Light Chain Levels May Be Useful Biomarker for Disease Progression in Parkinson’s, Study Finds

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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PD GENEration study

Levels of neurofilament light chain (NfL) — a protein found in blood plasma — may be a useful biomarker of disease progression for Parkinson’s, a study says.

The study, “Blood NfL: A biomarker for disease severity and progression in Parkinson disease,” was published in the journal Neurology.

A hallmark feature of Parkinson’s disease is the progressive degeneration of brain cells, which can happen at varying rates in different people. As such, researchers have focused on discovering a biomarker of neurodegeneration that could be used to predict the course of the disease for each individual patient.

The protein neurofilament light chain (NfL) is a key component of axons — myelinated nerve segments responsible for the transmission of nerve signals — and the main byproduct of nerve cell degeneration.

In other chronic neurodegenerative disorders — including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), inherited peripheral neuropathy, Alzheimer’s dementia, and frontotemporal dementia — studies have reported that the levels of NfL in blood plasma were abnormally high, suggesting its usefulness as a marker of neurodegeneration.

In the case of spinal muscular atrophy (SMA), a genetic neurodegenerative disorder that affects motor neurons, the phosphorylated neurofilament heavy subunit (pNF-H) — a key component of motor nerve cells — is also being investigated as a potential biomarker of neurodegeneration.

In this study, researchers from the National Taiwan University and their collaborators set out to investigate if plasma levels of NfL could also be associated with disease progression in people with Parkinson’s disease.

To that end, they carried out a prospective longitudinal study in which they followed 116 patients with Parkinson’s, 22 people with multiple system atrophy (MSA) — a rare neurodegenerative disorder — and 40 healthy individuals (controls).

Plasma levels of NfL were measured in all study participants using an electrochemiluminescence immunoassay — a technique that allows researchers to measure the levels of a protein of interest based on an electrochemical reaction. Researchers noted that the testing required just a blood sample from each participant.

Those who had Parkinson’s performed motor and cognitive tests at the beginning of the study, and at a mean follow-up interval of three years. The Unified Parkinson’s Disease Rating Scale (UPDRS) Part III and the Hoehn-Yahr scale were used to evaluate the progression of motor symptoms, while the Mini-Mental State Examination (MMSE) was used to assess the progression of cognitive symptoms.

Results showed that plasma levels of NfL were much higher among those with MSA (35.8 pg/mL), compared with those with Parkinson’s (17.6 pg/mL), and controls (10.6 pg/mL).

However, in patients with Parkinson’s, NfL levels were higher among those who had dementia and among those with severe motor impairments (advanced Hoehn-Yahr stage).

Correlation analyses revealed there was a modest association between NfL levels and UPDRS Part III (motor) scores.

Another statistical analysis performed after a mean follow-up of 3.4 years — and normalized for participants’ age, sex, disease duration and baseline symptoms, or symptoms at the start of the study — revealed that higher levels of NfL at baseline were linked to a higher risk of disease progression in patients with Parkinson’s. This was true for either motor or cognitive symptoms.

“Our results suggested that the plasma NfL level could serve as a noninvasive, easily accessible biomarker to assess disease severity and to monitor disease progression in PD,” the researchers said.

“Future large longitudinal follow-up studies that incorporate other biomarkers such as neuroimages are needed to strengthen the possible prognostic role of blood NfL levels in PD progression,” they added.