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- Lerche, S., et al.
(författare)
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CSF Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in PD and DLB
- 2021
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:11, s. 2595-2604
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Tidskriftsartikel (refereegranskat)abstract
- Background Molecular pathways associated with alpha-synuclein proteostasis have been detected in genetic studies and in cell models and include autophagy, ubiquitin-proteasome system, mitochondrial homeostasis, and synaptic plasticity. However, we lack biomarkers that are representative for these pathways in human biofluids. Objective The objective of this study was to evaluate CSF protein profiles of pathways related to alpha-synuclein proteostasis. Methods We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with alpha-synucleinopathy (385 PD patients and 67 DLB patients). We included 80 PD patients and 17 DLB patients with variants in the glucocerebrosidase gene to serve as proxy for accelerated alpha-synuclein pathology with pronounced clinical trajectories. Results (1) Proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy were lower in PD and DLB patients compared with healthy controls. (2) These patterns were more pronounced in DLB than in PD patients, accentuated by GBA variant status in both entities. (3) CSF levels of these proteins were positively associated with CSF levels of total alpha-synuclein, with lower levels of proteostasis proteins related to lower levels of total alpha-synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of alpha-synuclein longitudinally compared with PD patients with a normal proteostasis profile. Conclusion CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to alpha-synuclein proteostasis in PD and DLB. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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- Lerche, S, et al.
(författare)
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Methods in Neuroepidemiology Characterization of European Longitudinal Cohort Studies in Parkinson's Disease--Report of the JPND Working Group BioLoC-PD
- 2015
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 45:4, s. 282-297
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Enormous effort is being put into the identification and characterization of symptoms that may be used as predictive and progression markers in Parkinson's disease (PD). An impressive number of PD patients and individuals at risk for or in the prodromal stage of PD are currently followed in longitudinal studies; however, there does not exist an overview on the kind of markers evaluated and the assessments used. <b><i>Methods:</i></b> Information on the design, sample size, evaluated markers and assessments of 21 studies of the Joint Programme - Neurodegenerative Disease Research BioLoC-PD working group were collected by questionnaire. The studies were classified into at risk/prodromal or clinical PD cohorts. The assessments were grouped into quantitative assessments, investigator-rated assessments, investigator interviews, patient-rated questionnaires and caregiver-rated questionnaires. <b><i>Results:</i></b> Compilation of these data revealed an interesting consensus on evaluated markers, but there was an enormous variability of assessments. Furthermore, there is a remarkable similarity in the markers assessed and evaluation methods applied in the risk/prodromal and clinical PD cohorts. <b><i>Conclusions:</i></b> The inventory of the longitudinal cohorts that are part of the BioLoC-PD consortium reveals that there is a growing consensus on the markers that should be assessed in longitudinal cohort studies in PD. However, controversy still exists on the specific type of assessment. To allow comparison of data and common analyses it will be essential to harmonize scales and assessment outcomes.
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