Blood neurofilament light, Parkinson’s disease, Parkinsonism, and physical function in a longitudinal population study

Abstract

AbstractBackgroundBlood biomarkers of parkinsonism and Parkinson’s disease (PD) may allow for earlier identification of these conditions and improved longitudinal investigation of PD pathogenesis. Neurofilament light (Nf‐L), a neuronal cytoplasmic protein, is a biomarker of neurodegeneration measurable in CSF or blood. We examined the longitudinal association of serum Nf‐L with clinically diagnosed PD, parkinsonian signs, and physical functioning change over 16 years in a population‐based sample of Black and White older adults.MethodsData came from 1,327 older participants from the Chicago Health and Aging Project (CHAP), a longitudinal population‐based study of common chronic conditions of aging. Clinical evaluations included assessing parkinsonian signs in four domains, bradykinesia, parkinsonian gait, rigidity, and tremors using a structured version of the United Parkinson’s Disease Rating Scale. PD was diagnosed by board certified neurologists. Parkinsonian signs were reported as the four domain scores and a global parkinsonian score (combination of domain scores). Physical function was assessed by performance‐based tests. Serum Nf‐L was measured with an ultrasensitive immunoassay.ResultsAfter adjusting for demographic characteristics, the APOE‐e4 allele, and cognitive function, a 2‐fold higher concentration of serum Nf‐L was associated with the development of clinical PD (OR = 2.54, 95% CI: 1.70, 3.81), and global parkinsonian scores (OR = 2.44, 95% CI: 1.94, 2.94). This association was significant over five years before diagnosis. Compared to participants below 18.5 pg/mL of serum Nf‐L at baseline, participants in between 18.5–25.4 pg/mL, 25.4–37.3 pg/mL, and above 37.3 pg/mL had a higher odds ratio of clinical PD at all time intervals ranging from the time of diagnosis to greater than five years before diagnosis. A higher concentration of serum Nf‐L was associated with a faster decline in physical functioning over the duration of the study. In participants with 2‐fold higher concentrations of serum Nf‐L, the annual rate of decline in physical functioning increased by 0.15 units (95% CI: 0.21, 0.08).ConclusionsSerum Nf‐L predicted the development of clinically diagnosed PD, parkinsonian signs, and physical functioning decline in a population‐based sample. Our findings suggest that Nf‐L may serve as a potential biomarker for physical functioning outcomes in older adults.