scholarly journals Brain Atrophy Mediates the Relationship between Misfolded Proteins Deposition and Cognitive Impairment in Parkinson’s Disease

2021 ◽  
Vol 11 (8) ◽  
pp. 702
Author(s):  
Chiun-Chieh Yu ◽  
Chia-Yin Lu ◽  
Meng-Hsiang Chen ◽  
Yueh-Sheng Chen ◽  
Cheng-Hsien Lu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Atrophy ◽  
Misfolded Proteins ◽  
Misfolded Protein ◽  
Phosphorylated Tau ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Protein Levels ◽  
The Relationship

Parkinson’s disease is associated with cognitive decline, misfolded protein deposition and brain atrophy. We herein hypothesized that structural abnormalities may be mediators between plasma misfolded proteins and cognitive functions. Neuropsychological assessments including five domains (attention, executive, speech and language, memory and visuospatial functions), ultra-sensitive immunomagnetic reduction-based immunoassay (IMR) measured misfolded protein levels (phosphorylated-Tau, Amyloidβ-42 and 40, α-synuclein and neurofilament light chain) and auto-segmented brain volumetry using FreeSurfur were performed for 54 Parkinson’s disease (PD) patients and 37 normal participants. Our results revealed that PD patients have higher plasma misfolded protein levels. Phosphorylated-Tau (p-Tau) and Amyloidβ-42 (Aβ-42) were correlated with atrophy of bilateral cerebellum, right caudate nucleus, and right accumbens area (RAA). In mediation analysis, RAA atrophy completely mediated the relationship between p-Tau and digit symbol coding (DSC). RAA and bilateral cerebellar cortex atrophy partially mediated the Aβ-42 and executive function (DSC and abstract thinking) relationship. Our study concluded that, in PD, p-Tau deposition adversely impacts DSC by causing RAA atrophy. Aβ-42 deposition adversely impacts executive functions by causing RAA and bilateral cerebellum atrophy.

scholarly journals Temporal trajectory of biofluid markers in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Min Seok Baek ◽  
Myung Jun Lee ◽  
Han-Kyeol Kim ◽  
Chul Hyoung Lyoo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Amyloid Β ◽  
Rapid Progression ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Using Data ◽  
Negative Exponential ◽  
T Tau

AbstractFull dynamics of biofluid biomarkers have been unknown in patients with Parkinson’s disease (PD). Using data from 396 PD patients and 182 controls in the Parkinson's Progression Markers Initiative (PPMI) database, we estimated long-term temporal trajectories of CSF α-synuclein (α-syn), amyloid-β (Aβ), total tau (t-tau), phosphorylated tau (p-tau) and serum neurofilament light chain (NfL) by integrating function between the baseline levels and annual changes. At baseline, PD patients showed lower CSF α-syn, Aβ, t-tau and p-tau levels than those of the controls. In all PD patients, CSF α-syn and Aβ decreased in a negative exponential pattern before the onset of motor symptoms, whereas CSF t-tau and p-tau, and serum NfL increased. Patients with cognitive impairment exhibited faster decline of Aβ and α-syn and faster rise of t-tau, p-tau and NfL, when compared to those without. Similarly, low Aβ group showed earlier decline of α-syn, faster rise of t-tau, p-tau and NfL, and faster decline of cognitive performances, when compared to high Aβ group. Our results suggest that longitudinal changes in biomarkers can be influenced by cognitive impairment and Aβ burden at baseline. PD patients with Aβ pathology may be associated with early appearance of α-synuclein pathology, rapid progression of axonal degeneration and neurodegeneration, and consequently greater cognitive decline.

Serum neurofilament light chain levels reflect cortical neurodegeneration in de novo Parkinson's disease

2020 ◽  
Vol 74 ◽  
pp. 43-49 ◽  
Author(s):  
Frederic Sampedro ◽  
Rocío Pérez-González ◽  
Saul Martínez-Horta ◽  
Juan Marín-Lahoz ◽  
Javier Pagonabarraga ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Light Chain ◽  
De Novo ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Unraveling Pathophysiological Mechanisms of Parkinson’s Disease: Contribution of CSF Biomarkers

2020 ◽  
Vol 15 ◽  
pp. 117727192096407
Author(s):  
Lucia Farotti ◽  
Federico Paolini Paoletti ◽  
Simone Simoni ◽  
Lucilla Parnetti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical History ◽  
Substantial Contribution ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Disease Modifying Drugs ◽  
Precise Diagnosis ◽  
And Oxidative Stress

Diagnosis of Parkinson’s disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow for early and more precise diagnosis and provide information about prognosis. Developments in analytical chemistry allow for the detection of a large number of molecules in cerebrospinal fluid (CSF), which are known to be associated with the pathogenesis of PD. Given the pathophysiology of PD, CSF α-synuclein species have the strongest rationale for use, also providing encouraging preliminary results in terms of early diagnosis. In the field of classical Alzheimer’s disease (AD) biomarkers, low CSF Aβ42 levels have shown a robust prognostic value in terms of development of cognitive impairment. Other CSF biomarkers including lysosomal enzymes, neurofilament light chain, markers of neuroinflammation and oxidative stress, although promising, have not proved to be reliable for diagnostic and prognostic purposes yet. Overall, the implementation of CSF biomarkers may give a substantial contribution to the optimal use of disease-modifying drugs.

scholarly journals Gold-nanourchin complexed silicon dioxide-probe on gap-fingered interdigitated electrode surface for Parkinson’s Disease determination by current–volt measurement

2021 ◽  
Vol 11 ◽  
pp. 184798042098735
Author(s):  
Xiaohong Li ◽  
Wei Shi ◽  
Wenyan Zhang ◽  
Weiyao Chen ◽  
Dan Cao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Silicon Dioxide ◽  
Limit Of Detection ◽  
Detection System ◽  
Interdigitated Electrode ◽  
Limit Of Quantification ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Detection Range

Parkinson’s disease (PD) is a nervous disorder, affects physical movement, and leads to difficulty in balancing, walking, and coordination. A novel sensor is mandatory to determine PD and monitor the progress of the treatment. Neurofilament light chain (NfL) has been recognized as a good biomarker for PD and also helps to distinguish between PD and atypical PD syndromes. Immunosensor was generated by current–volt measurement on gap-fingered interdigitated electrode with silicon dioxide surface to determine NfL level. To enhance the detection, anti-NfL antibody was complexed with gold-nanourchin and immobilized on the sensing electrode. The current–volt response was gradually increased at the linear detection range from 100 fM to 1 nM. Limit of detection and sensitivity were 100 fM with the signal-to-noise ratio at n = 3 on a linear curve ( y = 0.081 x + 1.593; R 2 = 0.9983). Limit of quantification falls at 1 pM and high performance of the sensor was demonstrated by discriminating against other neurogenerative disease markers, in addition, it was reproducible even in serum-spiked samples. This method of detection system aids to measure the level of NfL and leads to determine the condition with PD.

scholarly journals Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

2020 ◽  
Author(s):  
Manuela Gries ◽  
Anne Christmann ◽  
Steven Schulte ◽  
Maximilian Weyland ◽  
Stephanie Rommel ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurofilament Light Chain ◽  
Treatment Interventions ◽  
Neurofilament Light ◽  
Early Biomarkers ◽  
Clinical Onset ◽  
Gait Parameters ◽  
Th 1 ◽  
Timely Treatment

AbstractParkinson’s disease (PD) usually has a late clinical onset. The lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use an α-synuclein-overexpressing transgenic (Th-1-SNCA-A30P) mouse model of PD to identify appropriate candidate markers in the gut for early stages of PD before hallmark symptoms begin to manifest. A30P mice did not show alterations in gait parameters at 2 months of age, and these mice were therefore defined as pre-symptomatic A30P mice (psA30P). We discovered early functional motility changes in the gut and early molecular dysregulations in the myenteric plexus of psA30P mice by comparative protein and miRNA profiling and cell culture experiments. We found that the proteins neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are potential biomarkers of early PD that may facilitate timely treatment and/or prevention of PD in men.

scholarly journals Assessing Plasma Levels of α-Synuclein and Neurofilament Light Chain by Different Blood Preparation Methods

2021 ◽  
Vol 13 ◽  
Author(s):  
Kuo-Hsuan Chang ◽  
Kou-Chen Liu ◽  
Chao-Sung Lai ◽  
Shieh-Yueh Yang ◽  
Chiung-Mei Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Light Chain ◽  
Plasma Levels ◽  
Room Temperature ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Preparation Methods ◽  
Different Types ◽  
Temperature Preparation

The potential biomarkers of Parkinson’s disease are α-synuclein and neurofilament light chain (NFL). However, inconsistent preanalytical preparation of plasma could lead to variations in levels of these biomarkers. Different types of potassium salts of EDTA and different centrifugation temperatures during plasma preparation may affect the results of α-synuclein and NFL measurements. In this study, we prepared plasma from eight patients with Parkinson’s disease (PD) and seven healthy controls (HCs) by using di- and tri-potassium (K2- and K3-) EDTA tubes and recruited a separated cohort with 42 PD patients and 40 HCs for plasma samples prepared from whole blood by centrifugation at room temperature and 4°C, respectively, in K2-EDTA tubes. The plasma levels of α-synuclein and NFL in K2- and K3-EDTA were similar. However, the levels of α-synuclein in the plasma prepared at 4°C (101.57 ± 43.43 fg/ml) were significantly lower compared with those at room temperature (181.23 ± 196.31 fg/ml, P < 0.001). Room temperature preparation demonstrated elevated plasma levels of α-synuclein in PD patients (256.6 ± 50.2 fg/ml) compared with the HCs (102.1 ± 0.66 fg/ml, P < 0.001), whereas this increase in PD was not present by preparation at 4°C. Both plasma preparations at room temperature and 4°C demonstrated consistent results of NFL, which are increased in PD patients compared with HCs. Our findings confirmed that K2- and K3-EDTA tubes were interchangeable for analyzing plasma levels of α-synuclein and NFL. Centrifugation at 4°C during plasma preparation generates considerable reduction and variation of α-synuclein level that might hinder the detection of α-synuclein level changes in PD.

scholarly journals Serum Neurofilament Light Chain as a Marker of Progression in Parkinson’s Disease: Long-Term Observation and Implications of Clinical Subtypes

2021 ◽  
pp. 1-14
Author(s):  
Emil Ygland Rödström ◽  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Oskar Hansson ◽  
Andreas Puschmann
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Light Chain ◽  
Progression Rate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Clinical Biomarkers ◽  
Combined Models

Background: Biochemical and clinical biomarkers correlate with progression rate and disease severity in Parkinson’s disease (PD) but are not sufficiently studied in late PD. Objective: To examine how serum neurofilament light chain (S-NfL) alone or combined with clinical classifications predicts PD outcome in later disease stages. Methods: Eighty-five patients with 7.9±5.1 years of PD duration were included in an observational cohort. Clinical scores were obtained at two separate examinations 8.2±2.0 years apart. S-NfL levels were determined with single molecule array (SiMoA). Five predefined disease progression milestones were assessed. After affirming combination potential of S-NfL and either of two clinical classifications, three combined models were constructed based on these factors and age at onset in different combinations. Results: S-NfL levels showed significant hazard ratios for four out of five disease progression milestones: walking-aid usage (HR 3.5; 95% CI 1.4–8.5), nursing home living (5.1; 2.1–12.5), motor end-stage (6.2; 2.1–17.8), and death (4.1; 1.7–9.7). Higher S-NfL levels were associated with lower ability in activities of daily living and poorer cognition at baseline and/or at follow-up. Combined models showed significantly improved area under receiver operating characteristic curves (0.77–0.91) compared to S-NfL levels alone (0.68–0.71) for predicting the five disease milestones. Conclusion: S-NfL levels stratified patients according to their likelihood to reach clinically relevant progression milestones during this long-term observational study. S-NfL alone reflected motor and social outcomes in later stages of PD. Combining S-NfL with clinical factors was possible and exploratory combined models improved prognostic accuracy.

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