Serum NFL levels predict progression of motor impairment and reduction in putamen dopamine transporter binding ratios in de novo Parkinson's disease: An 8-year longitudinal study

Ye, Rong; Locascio, Joseph J.; Goodheart, Anna E.; Quan, Moqing; Zhang, Baorong; Gomperts, Stephen N.

doi:10.1016/j.parkreldis.2021.02.008

Cited by 40 publications

(35 citation statements)

References 26 publications

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“…This finding is in line with a recent study reporting increased serum NfL levels in PIGD patients at earlier disease stages (Ng et al 2020). Furthermore, increased NfL levels predicted a more intense worsening of the PIGD, but not tremor score (Ye et al 2021). These findings suggest that a more pronounced neuro-axonal damage underlies PD symptoms of postural instability / gait difficulty.…”

Section: Discussionsupporting

confidence: 92%

“…However, the link between blood NfL with PIGD subtype and score in patients with advanced PD is unknown. Another recent study with 376 de novo PD patients from the PPMI database confirmed that higher serum NfL at baseline were associated with intense worsening of MDS-UPDRS III and PIGD scores, but not with progression of MoCA scores (Ye et al 2021).…”

Section: Introductionmentioning

confidence: 93%

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Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes of Parkinson’s disease in the MARK-PD study

et al. 2022

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The PIGD (postural instability / gait difficulty) subtype of Parkinson´s disease (PD) is associated with faster cognitive and motor decline. So far, there are no quantifiable biomarkers to aid clinical subtyping. Neurofilament light chain (NfL) is a highly specific marker of neuro-axonal damage and can be assessed in blood. Here, we investigated if serum NfL concentrations are associated with PIGD subtype and PIGD scores in PD patients at advanced disease stages. Furthermore, we evaluated if serum NfL is associated with motor and cognitive function assessed with MDS-UPDRS part III and Montreal cognitive assessment (MoCA). Serum NfL levels were analyzed with Single Molecule Assays (Simoa) in blood of 223 PD patients from the bioMARKers in Parkinson’s Disease (MARK-PD) study. Serum NfL concentrations were higher in PIGD patients independent of age, sex and disease duration. In linear regression analysis, serum NfL levels were associated with MoCA, MDS-UPDRS III and PIGD scores in unadjusted models, but remained significant after adjustment only with PIGD scores. In conclusion, increased serum NfL levels were associated with PIGD subtype and PIGD scores in patients with advanced PD.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 93%

Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes of Parkinson’s disease in the MARK-PD study

et al. 2022

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“…Higher baseline plasma levels of NfL were also associated with greater motor and cognitive decline after a follow-up period of 3 years in patients with PD, suggesting value of NfL as a predictive biomarker of disease severity and progression in this disease (Lin et al, 2019;Ma et al, 2021;Zhu et al, 2021). A recent study also suggests that higher serum NfL levels were also associated with dopamine transporter concentration (Ye et al, 2021).…”

Section: Parkinson's Diseasementioning

confidence: 95%

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

2021

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Biomarkers of neurodegeneration and neuronal injury have the potential to improve diagnostic accuracy, disease monitoring, prognosis, and measure treatment efficacy. Neurofilament proteins (NfPs) are well suited as biomarkers in these contexts because they are major neuron-specific components that maintain structural integrity and are sensitive to neurodegeneration and neuronal injury across a wide range of neurologic diseases. Low levels of NfPs are constantly released from neurons into the extracellular space and ultimately reach the cerebrospinal fluid (CSF) and blood under physiological conditions throughout normal brain development, maturation, and aging. NfP levels in CSF and blood rise above normal in response to neuronal injury and neurodegeneration independently of cause. NfPs in CSF measured by lumbar puncture are about 40-fold more concentrated than in blood in healthy individuals. New ultra-sensitive methods now allow minimally invasive measurement of these low levels of NfPs in serum or plasma to track disease onset and progression in neurological disorders or nervous system injury and assess responses to therapeutic interventions. Any of the five Nf subunits – neurofilament light chain (NfL), neurofilament medium chain (NfM), neurofilament heavy chain (NfH), alpha-internexin (INA) and peripherin (PRPH) may be altered in a given neuropathological condition. In familial and sporadic Alzheimer’s disease (AD), plasma NfL levels may rise as early as 22 years before clinical onset in familial AD and 10 years before sporadic AD. The major determinants of elevated levels of NfPs and degradation fragments in CSF and blood are the magnitude of damaged or degenerating axons of fiber tracks, the affected axon caliber sizes and the rate of release of NfP and fragments at different stages of a given neurological disease or condition directly or indirectly affecting central nervous system (CNS) and/or peripheral nervous system (PNS). NfPs are rapidly emerging as transformative blood biomarkers in neurology providing novel insights into a wide range of neurological diseases and advancing clinical trials. Here we summarize the current understanding of intracellular NfP physiology, pathophysiology and extracellular kinetics of NfPs in biofluids and review the value and limitations of NfPs and degradation fragments as biomarkers of neurodegeneration and neuronal injury.

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“…has been predicted by biological factors in this same sample of PWPD. For example, Ye et al (2021) found that the protein neurofilament light chain (NFC) predicted motor decline across the first 8 years postdiagnosis based on UPDRS Section III (clinical exam) and total UPDRS scores. Their report also indicated that NFC predicted greater motor decline in nontremor motor phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Progression of Self-Perceived Speech and Swallowing Impairment in Early Stage Parkinson's Disease: Longitudinal Analysis of the Unified Parkinson's Disease Rating Scale

Zhang

2022

J Speech Lang Hear Res

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Purpose: The purpose of this study was to investigate the presence and progression of self-perceived speech and swallowing impairments in newly diagnosed people with Parkinson's disease (PD) longitudinally across 6 years. Method: Longitudinal data from the Parkinson's Progression Markers Initiative were analyzed across six consecutive years in a cohort of 269 newly diagnosed people with PD, and a subset of those ( n = 211) who were assessed at every time point across the 6 years. Dependent variables included self-perceived ratings of speech and swallowing impairment severity from the Unified Parkinson's Disease Rating Scale. Patient-centered factors of age at diagnosis and motor phenotype were also assessed to determine if they were related to the change in self-perceived speech and swallowing impairments. Results: Overall, self-perceived speech and swallowing impairments were present in newly diagnosed people with PD, although over time, the degree of severity for both remained in the mild range. However, the rate of change over time was significant for perceived speech impairment, F (5.5, 1158.8) = 21.1, p < .001), and perceived swallowing impairment, F (5.2, 1082.6) = 8.6, p < .001. Changes for speech and swallowing impairment were both in the direction of progressive severity. There were no effects of age at diagnosis or motor phenotype on the degree of change for either speech or swallowing. Conclusions: Self-perceptions of speech and swallowing impairment changed significantly over time in newly diagnosed people with PD (PWPD). Consistent with existing literature, self-perceptions of speech impairment were rated as more severe than those of swallowing impairment. These findings reveal that even in the early years postdiagnoses, PWPD are experiencing changes to speech and swallowing function, albeit within the mildly severe range. The presence of self-perceived mild speech and swallowing impairments in the initial years postdiagnosis may support the need for intervention to improve and or sustain function over time.

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Serum NFL levels predict progression of motor impairment and reduction in putamen dopamine transporter binding ratios in de novo Parkinson's disease: An 8-year longitudinal study

Cited by 40 publications

References 26 publications

Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes of Parkinson’s disease in the MARK-PD study

Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes of Parkinson’s disease in the MARK-PD study

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

Progression of Self-Perceived Speech and Swallowing Impairment in Early Stage Parkinson's Disease: Longitudinal Analysis of the Unified Parkinson's Disease Rating Scale

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