The development of a drug or combination of drugs to slow or stop the progression of Parkinson's disease is the most important goal in this disease area. An understanding of the complex etiology and pathogenesis of the disorder is essential in this process. However, the current pathways to disease pathogenesis identified from the genetic causes of Parkinson's disease offer optimism in the sense that they appear to converge and interconnect rather than diverge. Problems include the limited applicability of current models and the ability to test drugs at the right dose in clinical trials with suitable end points. Trials conducted so far have provided some indication of a positive effect, although the mechanism underlying this is not yet known.
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Development and application of a clinical core data set for deep brain stimulation in Parkinson's disease, dystonia or tremor: from data collection to data exchange and data sharing.
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Institute of Clinical Epidemiology and Biometry, Julius-Maximilians-Universität Würzburg (JMU), Haus D7, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
Background: Comprehensive clinical data regarding factors influencing the individual disease course of patients with movement disorders treated with deep brain stimulation might help to better understand disease progression and to develop individualized treatment approaches.
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Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment.
Nat Commun
January 2025
Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment.
View Article and Find Full Text PDFThe genetics of neurodegenerative diseases is the genetics of age-related damage clearance failure.
Mol Psychiatry
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Department of Psychological Medicine and Clinical Neuroscience, Cardiff University, United Kingdom and UK Dementia Research Institute at Cardiff, Cardiff University, Cardiff, UK.
In this perspective we draw together the data from the genome wide association studies for Alzheimer's disease, Parkinson's disease and the tauopathies and reach the conclusion that in each case, most of the risk loci are involved in the clearance of the deposited proteins: in Alzheimer's disease, the microglial removal of Aβ, in the synucleinopathies, the lysosomal clearance of synuclein and in the tauopathies, the removal of tau protein by the ubiquitin proteasome. We make the point that most loci identified through genome wide association studies are not strictly pathogenic but rather relate to failures to remove age related damage. We discuss these issues in the context of copathologies in elderly individuals and the prediction of disease through polygenic risk score analysis at different ages.
View Article and Find Full Text PDFFilipinos and Parkinson's disease: A scoping review of the literature.
Parkinsonism Relat Disord
January 2025
The Queen's Medical Center, 1301 Punchbowl Street, Honolulu, HI 96813, USA; University of Hawai'i at Manoa, John A. Burns School of Medicine, 651 Ilalo Street, Honolulu, HI 96813, USA.
Background: Filipinos are the third largest sub-group of Asian Americans in the United States and have greater socioeconomic and health disparities than many other Asian sub-groups [1,2,3,4,5,6,7,8]. Characteristics of Filipino patients with Parkinson's disease (PD) have not been adequately studied.
Objective: To scope the extent, range and nature of current knowledge on PD in Filipino-American (FA) patients in contrast to Filipino patients in general.
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Parkinsonism Relat Disord
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Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy; IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy.
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