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

Dutke, Janina; Lezius, Susanne; Buhmann, Carsten; Schulz, Robert; Gerloff, Christian; Kuhle, Jens; Choe, Chi‐un

doi:10.1007/s00702-022-02464-x

Cited by 10 publications

(8 citation statements)

References 25 publications

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“…These neurochemical and neuropathological findings correlate with a faster motor decline in PIGD patients. In line with these findings, blood NfL was higher in advanced PD patients with the PIGD subtype independent of age, sex and disease duration in a single-centre in Singapore and in the MARK-PD study from Hamburg (Ng et al 2020;Potter-Nerger et al 2022). However, baseline blood NfL levels did not differ between PIGD and TD subtypes at early disease stages, i.e.…”

Section: Blood Nfl and Parkinson Subtypessupporting

confidence: 74%

Blood neurofilament light chain in Parkinson’s disease

2023

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Blood neurofilament light chain (NfL) is an easily accessible, highly sensitive and reliable biomarker for neuroaxonal damage. Currently, its role in Parkinson’s disease (PD) remains unclear. Here, we demonstrate that blood NfL can distinguish idiopathic PD from atypical parkinsonian syndromes (APS) with high sensitivity and specificity. In cross-sectional studies, some found significant correlations between blood NfL with motor and cognitive function, whereas others did not. In contrast, prospective studies reported very consistent associations between baseline blood NfL with motor progression and cognitive worsening. Amongst PD subtypes, especially postural instability and gait disorder (PIGD) subtype, symptoms and scores are reliably linked with blood NfL. Different non-motor PD comorbidities have also been associated with high blood NfL levels suggesting that the neuroaxonal damage of the autonomic nervous system as well as serotonergic, cholinergic and noradrenergic neurons is quantifiable. Numerous absolute NfL cutoff levels have been suggested in different cohort studies; however, validation across cohorts remains weak. However, age-adjusted percentiles and intra-individual blood NfL changes might represent more valid and consistent parameters compared with absolute NfL concentrations. In summary, blood NfL has the potential as biomarker in PD patients to be used in clinical practice for prediction of disease severity and especially progression.

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Section: Blood Nfl and Parkinson Subtypessupporting

confidence: 74%

Blood neurofilament light chain in Parkinson’s disease

2023

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“…Moreover, the diffuse malignant phenotype was associated with a higher extent of atrophy in cerebral magnet resonance imaging (Fereshtehnejad et al 2017 ). The authors of a recent German study reported that serum NLF levels were increased in the PIGD subgroup and that NFL levels significantly correlated with the Montreal cognitive assessment (MoCA) scale and the MDS-UPDRS part III in PIGD patients (Pötter-Nerger et al 2022 ), emphasizing the diagnostic value of this biomarker.…”

Section: Diagnostic and Pathophysiological Aspects Of Parkinson’s Dis...mentioning

confidence: 99%

Disease modification in Parkinsonism: obstacles and ways forward

2022

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To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs.

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“…Blood NfL was also found associated with PIGD-subtype of PD (Pötter-Nerger et al 2022 ; Ng et al 2020 ). At 2 year follow-up, NfL levels were higher in PIGD compared to tremor-dominant subtype, and within the PIGD group, higher blood NfL was associated with worse global cognition and UPDRS III at baseline and predicted motor and cognitive decline (Ng et al 2020 ).…”

Section: Blood-based Biomarkermentioning

confidence: 99%

Blood-based biomarker in Parkinson’s disease: potential for future applications in clinical research and practice

et al. 2022

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The clinical presentation of Parkinson’s disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view. Various tissue- and fluid-based biomarkers are currently being investigated to improve the description of PD. From a clinician's perspective, signatures from blood that are relatively easy to obtain would have great potential for use in clinical practice if they fulfill the necessary requirements as PD biomarker. In this review article, we summarize the knowledge on blood-based PD biomarkers and present both a researcher’s and a clinician’s perspective on recent developments and potential future applications.

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

Cited by 10 publications

References 25 publications

Blood neurofilament light chain in Parkinson’s disease

Blood neurofilament light chain in Parkinson’s disease

Disease modification in Parkinsonism: obstacles and ways forward

Blood-based biomarker in Parkinson’s disease: potential for future applications in clinical research and practice

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