Blood Biomarker Linked With Parkinson's Disease

Serum neurofilament light (NfL), a measure of axonal injury, was associated with incident Parkinson's disease, parkinsonian signs, and decline in physical functioning, a longitudinal study showed.

Among 1,300 people in the Chicago Health and Aging Project (CHAP), a twofold higher concentration of serum NfL was associated with incident clinical Parkinson's disease (OR 2.54, 95% CI 1.70-3.81), according to Shannon Halloway, PhD, RN, of Rush University Medical Center in Chicago, and co-authors.

Compared with people in the lowest quartile of serum NfL at baseline, those with higher concentrations had greater odds of clinical Parkinson's disease at all time points, ranging from the date of diagnosis to more than 5 years earlier, the researchers reported in Neurology.

"This study confirms the potential of NfL to detect a neurological disease years before the clinical picture becomes manifest, even in the case of Parkinson's disease where cerebrospinal fluid (CSF) and blood NfL do not clearly peak in the clinical phase as in other central nervous system (CNS) degenerative diseases," wrote Lorenzo Gaetani, MD, PhD, and Lucilla Parnetti, MD, PhD, both of the University of Perugia in Italy, in an accompanying editorial.

In recent years, ultrasensitive immunoassays have made it possible to measure NfL in serum and plasma, they observed. "This sentinel of neuronal damage has been shown to detect the presence of a variety of CNS diseases, from multiple sclerosis to Alzheimer's disease, frontotemporal dementia, motor neuron diseases, parkinsonisms, cerebrovascular disease, and traumatic brain injury," they noted.

"Due to its ability to reflect the dynamic nature of CNS injuries, NfL has been called the C-reactive protein of neurology," Gaetani and Parnetti wrote. In a hypothetical future scenario, serum NfL might be a first test, which would be followed by more disease-specific blood or CSF analyses, they added.

Halloway and co-authors studied 1,327 people over age 65 who were enrolled in six triennial cycles of the CHAP cohort study from 1993 to 2012. Blood samples were collected from 1994 to 2012, at both study entry and over time.

Clinical evaluations included assessing parkinsonian signs in four domains -- bradykinesia, parkinsonian gait, rigidity, and tremors -- using a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS). Performance tests evaluated physical functioning, which were scored 0-15, with lower scores indicating potential inability to conduct tasks of independent living. Board-certified neurologists diagnosed Parkinson's disease.

At baseline, participants had an average age of about 74; 62% were women, and 61% were Black. Baseline serum NfL ranged from 0.99 to 755 pg/mL. The highest quartile had NfL values greater than 37.3 pg/mL; in the lowest quartile, NfL was less than 18.5 pg/mL.

During the study, 77 people (6.1%) were diagnosed with clinical Parkinson's disease. Parkinsonian signs were 9.5 on average (range 0-66).

People with NfL values in the highest quartile at baseline had a significantly higher risk of subsequently developing Parkinson's disease compared with those with NfL in the lowest quartile (OR 3.74, 95% CI 1.75-8.0).

Among people with twofold higher concentrations of serum NfL at baseline, the annual rate of physical functioning decline increased by 0.15 units.

People with twofold higher NfL concentrations were also more likely to have parkinsonian signs (OR 2.44, 95% CI 1.94-2.94). There was a significant graded association with parkinsonian signs in all domains in the third (25.4 to 37.3 pg/mL) and fourth NfL quartile.

Findings from the analysis may be limited, the researchers acknowledged. The sample represented a biracial cohort in metropolitan Chicago, and results may not apply to other groups. The neuropathological development of Parkinson's disease may begin in earlier periods not captured in this study. In addition, the recruitment timeline of the study spanned 16 years, which may have resulted in variability of Parkinson's diagnoses over time.

Comment