Patients with high levels of serum neurofilament light (NfL) were more likely to be diagnosed with incident Parkinsons disease or parkinsonian signs, according to a new study published in the journal Neurology.¹

A total of 1327 participants aged 65 years and older (average age 74 years) who were enrolled in the Chicago Health and Aging Project (CHAP) study from 1993 to 2012 were included in the present study with an objective to study whether baseline levels of serum Nf-L could facilitate earlier diagnosis of Parkinson’s disease (PD) or detection of parkinsonian signs or its association with changes in physical functioning over a period of 16 years. The United Parkinson’s Disease Rating Scale was used to assess parkinsonian signs (bradykinesia, parkinsonian gait, rigidity and tremors). Participants were subject to Performance tests to assess their ability to independently carry out Activities of daily living. Serum levels of Nf-L were measured with an ultrasensitive immunoassay method. The baseline levels ranged from 0.99-755 pg/mL. Those in the highest quartile had levels >37.3 pg/mL, while those in the lowest quartile had levels <18.5 pg/mL.

Seventy-seven participants developed incident clinical Parkinsons disease during the course of the study. Results showed that a 2-folds increase in the serum levels of NfL doubled the risk of developing incident clinical Parkinsons disease with an odds ratio of 2.54. The probability of parkinsonian signs was also higher with OR 2.44 after adjusting for demographics, global cognition and the APOE-e4 allele.

Participants who had serum Nf-L ranging between 18.5 and 25.4 pg/mL, 25.4 and 37.3 pg/mL and greater than 37.3 pg/mL were at greater risk of being diagnosed with clinical Parkinsons disease “at all time intervals ranging from the time of diagnosis to greater than five years before diagnosis”. Those with baseline NfL levels in the highest quartile had 3.74 higher odds of developing Parkinsons disease later on compared to participants with Nf-L in the lowest quartile.

The rate of decline in physical functioning was faster in patients with high serum Nf-L levels. It increased by 0.15 units annually among patients in whom the serum NfL levels doubled from the baseline values.

These findings have clinical implications and suggest that serum Nf-L, “a neuronal cytoplasmic protein”, may serve “as a potential biomarker for neurodegeneration” and facilitate earlier detection of Parkinson’s disease, including other neurodegenerative diseases, even before they become clinically evident.

Reference

1. Halloway S, et al; Chicago Health and Aging Project. Association of neurofilament light with the development and severity of Parkinson Disease. Neurology. 2022 Apr 13:10.1212/WNL.0000000000200338. doi: 10.1212/WNL.0000000000200338.