NfL Levels in Blood Vesicles May Mirror Severity of Motor Symptoms

Higher levels of neurofilament light chain (NfL) — a biomarker of nerve cell damage — inside small vesicles in the blood associate with more severe motor symptoms, particularly slow movement and rigidity, in people with Parkinson’s disease, a small study suggests.

However, no significant changes in NfL levels inside these vesicles, called exosomes, were observed between Parkinson’s patients and healthy individuals.

Future studies analyzing these levels in a larger group of patients and over time are needed to confirm whether this biomarker may be used to assess Parkinson’s severity and neurodegeneration, the researchers noted.

The study, “Neurofilament light chain level in plasma extracellular vesicles and Parkinson’s disease,” was published in the journal Therapeutic Advances in Neurological Disorders.

A major structural protein of nerve cell fibers (axons), NfL is released into the blood when neurons and axons are damaged. As such, the protein is commonly used as a marker of neurologic damage.

“An increase of NfL levels in the CSF and blood reflects the degree of axonal damage in neurological diseases of different [causes], including inflammatory, traumatic, degenerative, and cerebrovascular,” the researchers wrote. Of note, the CSF is the fluid that bathes the brain and spinal cord.

NfL levels, either in the blood or in the CSF, are typically found at higher levels among Parkinson’s patients, compared with healthy individuals, and are associated with disease progression.

In particular, a previous study showed that NfL blood levels were linked to the severity of Parkinson’s symptoms — both motor and non-motor — indicating that a blood test measuring NfL levels may be a useful way to measure disease progression in this patient population.

Measuring proteins in exosomes, tiny vesicles naturally produced by neurons and other cells, has gain in interest in recent years. Their content often mirrors the state of the cell, and evidence suggests that the release of exosomes filled with abnormal or disease-associated proteins may be an early indicator of disease onset or progression.

In agreement, previous studies have suggested that the levels of alpha-synuclein — a hallmark of Parkinson’s disease — in these vesicles may help diagnose early Parkinson’s and identify patients with different types of this disease.

Now, researchers at the Shuang-Ho Hospital, in Taiwan, evaluated the potential association between NfL levels in blood exosomes and Parkinson’s.

They analyzed blood samples from 116 people with mild to moderate Parkinson’s and 46 people without the disorder, dementia, or other neurodegenerative diseases (used as the control group).

All participants, recruited at the hospital, underwent cognitive function assessment. Disease severity was determined in patients using the Unified Parkinson’s Disease Rating Scale (UPDRS), and within Part III of the UPDRS (which assess motor function) akinetic rigidity and tremor scores were also calculated.

Akinetic rigidity symptoms include slow movement accompanied by muscle stiffness. Compared with tremor, akinetic rigidity is associated with rapid disease progression and more severe alpha-synuclein-related damage.

Those with Parkinson’s were slightly older (69.7 vs. 67 years) and a greater proportion were women (53.4% vs. 39.1%) than those in the control group, but these differences were not statistically significant.

Patients had been living with the disease for a mean of 2.7 years, and showed significantly worse cognitive function than control individuals.

Notably, no significant differences in exosome-associated NfL levels were observed between these two groups.

However, among Parkinson’s patients, these levels were significantly associated with akinetic rigidity scores, with higher NfL levels being linked to more severe motor symptoms. No significant associations were found between NfL levels and age, disease duration, severity of overall motor symptoms and of tremor, and cognitive function.

The team then divided patients into four groups based on their exosome-associated NfL levels. After adjusting for age, sex, and disease duration to minimize their influence, they found that patients with the lowest levels had significantly lower UPDRS and akinetic rigidity scores, reflecting less severe motor symptoms.

“The association between the [lowest NfL levels] and mild severity of motor symptoms, especially akinetic rigidity, indicates the possible association of [blood exosomes] NfL with the severity of neurodegeneration in [Parkinson’s disease],” the researchers wrote.

They also noted that the observed link with akinetic rigidity in particular may stem from the greater neurologic damage seen in patients with these symptoms, potentially increasing the release of NfL through exosomes.

Larger studies monitoring NfL exosome levels in Parkinson’s patients over time are needed to further validate these potential associations, the team noted.