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Parkinson Disease: HELP
Articles from Amsterdam
Based on 232 articles published since 2008
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These are the 232 published articles about Parkinson Disease that originated from Amsterdam during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Review Clinical utility of FDG PET in Parkinson's disease and atypical parkinsonism associated with dementia. 2018

Walker, Zuzana / Gandolfo, Federica / Orini, Stefania / Garibotto, Valentina / Agosta, Federica / Arbizu, Javier / Bouwman, Femke / Drzezga, Alexander / Nestor, Peter / Boccardi, Marina / Altomare, Daniele / Festari, Cristina / Nobili, Flavio / Anonymous2310976. ·Division of Psychiatry, University College London, London, UK. z.walker@ucl.ac.uk. · St Margaret's Hospital, Essex Partnership University NHS Foundation Trust, Epping, CM16 6TN, UK. z.walker@ucl.ac.uk. · Alzheimer Operative Unit, IRCCS S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy. · Division of Nuclear Medicine and Molecular Imaging, Department of Medical Imaging, University Hospitals of Geneva, Geneva University, Geneva, Switzerland. · Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. · Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, Pamplona, Spain. · Department of Neurology & Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. · Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne and German Center for Neurodegenerative Diseases (DZNE), Cologne, Germany. · German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. · Queensland Brain Institute, University of Queensland and the Mater Hospital, Brisbane, Australia. · LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of Psychiatry, University of Geneva, Geneva, Switzerland. · LANE - Laboratory of Alzheimer's Neuroimaging & Epidemiology, IRCCS S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy. · Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. · Department of Neuroscience (DINOGMI), University of Genoa & Clinical Neurology Polyclinic IRCCS San Martino-IST, Genoa, Italy. flaviomariano.nobili@hsanmartino.it. ·Eur J Nucl Med Mol Imaging · Pubmed #29779045.

ABSTRACT: PURPOSE: There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson's disease (PD) at risk of future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome. METHODS: We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion. RESULTS: Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility. CONCLUSION: Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia.

2 Review The neurobiology of impulse control disorders in Parkinson's disease: from neurotransmitters to neural networks. 2018

Vriend, Chris. ·Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands. c.vriend@vumc.nl. · Department of Anatomy & Neurosciences, VU University Medical Center, p/a sec. ANW O|2, PO Box 7007, 1007MB BT, Amsterdam, the Netherlands. c.vriend@vumc.nl. · Amsterdam Neuroscience, Amsterdam, The Netherlands. c.vriend@vumc.nl. ·Cell Tissue Res · Pubmed #29383446.

ABSTRACT: Impulse control disorders (ICD) are common neuropsychiatric disorders that can arise in Parkinson's disease (PD) patients after commencing dopamine replacement therapy. Approximately 15% of all patients develop these disorders and many more exhibit subclinical symptoms of impulsivity. ICD is thought to develop due to an interaction between the use of dopaminergic medication and an as yet unknown neurobiological vulnerability that either pre-existed before PD onset (possibly genetic) or is associated with neural alterations due to the PD pathology. This review discusses genes, neurotransmitters and neural networks that have been implicated in the pathophysiology of ICD in PD. Although dopamine and the related reward system have been the main focus of research, recently, studies have started to look beyond those systems to find new clues to the neurobiological underpinnings of ICD and come up with possible new targets for treatment. Studies on the whole-brain connectome to investigate the global alterations due to ICD development are currently lacking. In addition, there is a dire need for longitudinal studies that are able to disentangle the contributions of individual (genetic) traits and secondary effects of the PD pathology and chronic dopamine replacement therapy to the development of ICD in PD.

3 Review Diagnostic utility of cerebrospinal fluid α-synuclein in Parkinson's disease: A systematic review and meta-analysis. 2017

Eusebi, Paolo / Giannandrea, David / Biscetti, Leonardo / Abraha, Iosief / Chiasserini, Davide / Orso, Massimiliano / Calabresi, Paolo / Parnetti, Lucilla. ·Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy. · Health Planning Service, Regional Health Authority of Umbria, Department of Epidemiology, Perugia, Italy. · Neurology Unit, Department of Specialist Medicine, USL Umbria 1 North area, Gubbio and Gualdo Tadino Hospital, Gubbio, Italy. · Oncoproteomics Laboratory, VU University Medical Center, Amsterdam, The Netherlands. · IRCCS Fondazione Santa Lucia, Rome, Italy. ·Mov Disord · Pubmed #28880418.

ABSTRACT: BACKGROUND: The accumulation of misfolded α-synuclein aggregates is associated with PD. However, the diagnostic value of the α-synuclein levels in CSF is still under investigation. METHODS: A comprehensive search of the literature was performed, yielding 34 studies eligible for meta-analysis. We included studies that reported data on CSF total, oligomeric and phosphorylated α-synuclein in patients with PD and healthy participants, neurological controls, or other parkinsonisms. Standardized mean differences were pooled using random-effects models, and heterogeneity was reported as I RESULTS: Concentrations of α-synuclein species in PD did not show significant differences with respect to the levels found in other parkinsonisms. Total α-synuclein was significantly reduced in PD when compared with controls (standardized mean differences -0.48; P < .001, I CONCLUSION: Most of the studies were at high risk of bias and have concerns regarding applicability. Diagnostic performance of CSF α-synuclein species is still below what would be considered acceptable for their introduction in clinical practice. Future research should focus on combining α-synuclein species with other biochemical markers as well on improving the standardization of current assays. © 2017 International Parkinson and Movement Disorder Society.

4 Review Therapeutic potential of autophagy-enhancing agents in Parkinson's disease. 2017

Moors, Tim E / Hoozemans, Jeroen J M / Ingrassia, Angela / Beccari, Tommaso / Parnetti, Lucilla / Chartier-Harlin, Marie-Christine / van de Berg, Wilma D J. ·Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. t.moors@vumc.nl. · Department of Pathology, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. · Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy, Amsterdam Neuroscience, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. · Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy. · Department of Medicine, Section of Neurology, University of Perugia, Perugia, Italy. · UMR-S 1172-JPArc-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, University of Lille, Lille, F-59000, France. · Inserm, UMR-S 1172, Team "Early stages of Parkinson's disease", F-59000, Lille, France. ·Mol Neurodegener · Pubmed #28122627.

ABSTRACT: Converging evidence from genetic, pathological and experimental studies have increasingly suggested an important role for autophagy impairment in Parkinson's Disease (PD). Genetic studies have identified mutations in genes encoding for components of the autophagy-lysosomal pathway (ALP), including glucosidase beta acid 1 (GBA1), that are associated with increased risk for developing PD. Observations in PD brain tissue suggest an aberrant regulation of autophagy associated with the aggregation of α-synuclein (α-syn). As autophagy is one of the main systems involved in the proteolytic degradation of α-syn, pharmacological enhancement of autophagy may be an attractive strategy to combat α-syn aggregation in PD. Here, we review the potential of autophagy enhancement as disease-modifying therapy in PD based on preclinical evidence. In particular, we provide an overview of the molecular regulation of autophagy and targets for pharmacological modulation within the ALP. In experimental models, beneficial effects on multiple pathological processes involved in PD, including α-syn aggregation, cell death, oxidative stress and mitochondrial dysfunction, have been demonstrated using the autophagy enhancers rapamycin and lithium. However, selectivity of these agents is limited, while upstream ALP signaling proteins are involved in many other pathways than autophagy. Broad stimulation of autophagy may therefore cause a wide spectrum of dose-dependent side-effects, suggesting that its clinical applicability is limited. However, recently developed agents selectively targeting core ALP components, including Transcription Factor EB (TFEB), lysosomes, GCase as well as chaperone-mediated autophagy regulators, exert more specific effects on molecular pathogenetic processes causing PD. To conclude, the targeted manipulation of downstream ALP components, rather than broad autophagy stimulation, may be an attractive strategy for the development of novel pharmacological therapies in PD. Further characterization of dysfunctional autophagy in different stages and molecular subtypes of PD in combination with the clinical translation of downstream autophagy regulation offers exciting new avenues for future drug development.

5 Review Intestinal dysfunction in Parkinson's disease: Lessons learned from translational studies and experimental models. 2016

Pellegrini, C / Colucci, R / Antonioli, L / Barocelli, E / Ballabeni, V / Bernardini, N / Blandizzi, C / de Jonge, W J / Fornai, M. ·Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy. · Department of Pharmacy, University of Parma, Parma, Italy. · Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. ·Neurogastroenterol Motil · Pubmed #27611012.

ABSTRACT: BACKGROUND: Symptoms of digestive dysfunction in patients with Parkinson's disease (PD) occur at all stages of the disease, often preceding the onset of central motor symptoms. On the basis of these PD-preceding symptoms it has been proposed that PD could initiate in the gut, and that the presence of alpha-synuclein aggregates, or Lewy bodies in the enteric nervous system might represent one of the earliest signs of the disease. Following this hypothesis, much research has been focused on the digestive tract to unravel the mechanisms underlying the onset and progression of PD, with particular attention to the role of alterations in enteric neurotransmission in the pathophysiology of intestinal motility disturbances. There is also evidence suggesting that the development of central nigrostriatal neurodegeneration is associated with the occurrence of gut inflammation, characterized by increments of tissue pro-inflammatory markers and oxidative stress, which might support conditions of bowel neuromotor abnormalities. PURPOSE: The present review intends to provide an integrated and critical appraisal of the available knowledge on the alterations of enteric neuromuscular pathways regulating gut motor activity both in humans and preclinical models of PD. Moreover, we will discuss the possible involvement of neuro-immune mechanisms in the pathophysiology of aberrant gastrointestinal gut transit and neuromuscular activity in the small and large bowel.

6 Review Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease. 2016

Mahlknecht, Philipp / Pechlaner, Raimund / Boesveldt, Sanne / Volc, Dieter / Pinter, Bernardette / Reiter, Eva / Müller, Christoph / Krismer, Florian / Berendse, Henk W / van Hilten, Jacobus J / Wuschitz, Albert / Schimetta, Wolfgang / Högl, Birgit / Djamshidian, Atbin / Nocker, Michael / Göbel, Georg / Gasperi, Arno / Kiechl, Stefan / Willeit, Johann / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom. · Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands. · Divisions of Human Nutrition, Wageningen University, Wageningen, The Netherlands. · Study Center Confraternitaet-PKJ Vienna, Vienna, Austria. · Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. · Department of Applied Systems Research and Statistics, Johannes Kepler University Linz, Linz, Austria. · Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. klaus.seppi@uki.at. ·Mov Disord · Pubmed #27159493.

ABSTRACT: INTRODUCTION: The aim of this study was to evaluate odor identification testing as a quick, cheap, and reliable tool to identify PD. METHODS: Odor identification with the 16-item Sniffin' Sticks test (SS-16) was assessed in a total of 646 PD patients and 606 controls from three European centers (A, B, and C), as well as 75 patients with atypical parkinsonism or essential tremor and in a prospective cohort of 24 patients with idiopathic rapid eye movement sleep behavior disorder (center A). Reduced odor sets most discriminative for PD were determined in a discovery cohort derived from a random split of PD patients and controls from center A using L1-regularized logistic regression. Diagnostic accuracy was assessed in the rest of the patients/controls as validation cohorts. RESULTS: Olfactory performance was lower in PD patients compared with controls and non-PD patients in all cohorts (each P < 0.001). Both the full SS-16 and a subscore of the top eight discriminating odors (SS-8) were associated with an excellent discrimination of PD from controls (areas under the curve ≥0.90; sensitivities ≥83.3%; specificities ≥82.0%) and from non-PD patients (areas under the curve ≥0.91; sensitivities ≥84.1%; specificities ≥84.0%) in all cohorts. This remained unchanged when patients with >3 years of disease duration were excluded from analysis. All 8 incident PD cases among patients with idiopathic rapid eye movement sleep behavior disorder were predicted with the SS-16 and the SS-8 (sensitivity, 100%; positive predictive value, 61.5%). CONCLUSIONS: Odor identification testing provides excellent diagnostic accuracy in the distinction of PD patients from controls and diagnostic mimics. A reduced set of eight odors could be used as a quick tool in the workup of patients presenting with parkinsonism and for PD risk indication. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

7 Review Lysosomal Dysfunction and α-Synuclein Aggregation in Parkinson's Disease: Diagnostic Links. 2016

Moors, Tim / Paciotti, Silvia / Chiasserini, Davide / Calabresi, Paolo / Parnetti, Lucilla / Beccari, Tommaso / van de Berg, Wilma D J. ·Department of Anatomy and Neurosciences, Section Quantitative Morphology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. · Department of Pharmaceutical Sciences, Section of Nutrition and Food Science, University of Perugia, Perugia, Italy. · Department of Medicine, Section of Neurology, University of Perugia, Perugia, Italy. · Fondazione Santa Lucia-Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy. ·Mov Disord · Pubmed #26923732.

ABSTRACT: Lysosomal impairment is increasingly recognized as a central event in the pathophysiology of PD. Genetic associations between lysosomal storage disorders, including Gaucher disease and PD, highlight common risk factors and pathological mechanisms. Because the autophagy-lysosomal system is involved in the intralysosomal hydrolysis of dysfunctional proteins, lysosomal impairment may contribute to α-synuclein aggregation in PD. The degradation of α-synuclein is a complex process involving different proteolytic mechanisms depending on protein burden, folding, posttranslational modifications, and yet unknown factors. In this review, evidence for lysosomal dysfunction in PD and its intimate relationship with α-synuclein aggregation are discussed, after which the question of whether lysosomal proteins may serve as diagnostic biomarkers for PD is addressed. Changes in lysosomal enzymes, such as reduced glucocerebrosidase and cathepsin levels, have been observed in affected brain regions in PD patients. The detection of lysosomal proteins in CSF may provide a read-out of lysosomal dysfunction in PD and holds promise for the development of diagnostic PD biomarkers. Initial PD biomarker studies demonstrated altered lysosomal enzyme activities in CSF of PD patients when compared with controls. However, CSF lysosomal enzyme activities alone could not discriminate between PD patients and controls. The combination of CSF lysosomal markers with α-synuclein species and indicators of mitochondrial dysfunction, inflammation, and other pathological proteins in PD may be able to facilitate a more accurate diagnosis of PD. Further CSF biomarker studies are needed to investigate the utility of CSF lysosomal proteins as measures of disease state and disease progression in PD. © 2016 International Parkinson and Movement Disorder Society.

8 Review Systematic Review of the Relationship between Vitamin D and Parkinson's Disease. 2016

Rimmelzwaan, Lisanne M / van Schoor, Natasja M / Lips, Paul / Berendse, Henk W / Eekhoff, Elisabeth M W. ·Department of Internal Medicine section Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. · Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. · Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands. ·J Parkinsons Dis · Pubmed #26756741.

ABSTRACT: BACKGROUND: Although vitamin D may have both protective and symptomatic effects in Parkinson's disease (PD), the evidence is scarce and not well understood. Also, 25-hydroxyvitamin D (vitamin D) is suggested to play a neuroprotective and neurotrophic role in the brain. Therefore, this review investigates the relationship between vitamin D and PD. OBJECTIVE: Investigate the evidence for a relationship between vitamin D and PD by summarizing observational and interventional studies in humans, as well as relevant experimental studies. METHODS: A systematic search was made in the Medline, Cochrane and Embase databases (from inception to March 2014). All identified titles were independently evaluated by two reviewers. Articles were selected based on the presence of PD-related outcome data. Included were observational studies (including genetic studies) and interventional studies in humans, as well as relevant animal studies. RESULTS: A total of 20 studies (14 observational, 1 interventional and 5 rodent studies) were selected for analysis. Eight observational studies showed that serum 25(OH) D levels tend to be low in PD. One observational study indicated that low serum 25(OH) D may worsen automatic postural responses and one interventional study suggested that vitamin D supplementation can prevent worsening (based on the Hoehn and Yahr rating scale). Studies in rodent models of PD showed a protective effect of vitamin D treatment on dopaminergic neurons in the substantia nigra. Results of genetic studies on the association between vitamin D receptor polymorphisms and the risk of PD were contradictory. CONCLUSION: The literature supports possible protective and symptomatic effects of vitamin D in PD. However, more observational and interventional studies in humans are needed to confirm and further elucidate the suggested beneficial effect of vitamin D on PD.

9 Review Apathy in Parkinson's disease: A systematic review and meta-analysis. 2015

den Brok, Melina G H E / van Dalen, Jan Willem / van Gool, Willem A / Moll van Charante, Eric P / de Bie, Rob M A / Richard, Edo. ·Department of Neurology, Academic Medical Center Amsterdam, The Netherlands. · Department of General Practise, Academic Medical Center Amsterdam, The Netherlands. · Department of Neurology, Radboud University Medical Center Nijmegen, The Netherlands. ·Mov Disord · Pubmed #25787145.

ABSTRACT: Apathy is a frequently reported neuropsychiatric symptom in Parkinson's disease (PD), but its prevalence and clinical correlates are debated. We aimed to address these issues by conducting a systematic review and meta-analysis. Embase, Medline/PubMed, and PsychINFO databases were searched for relevant studies. Data were extracted by two independent observers, using predefined extraction forms tailored specifically to the research question. From 1,702 titles and abstracts, 23 studies were selected. Meta-analysis showed a prevalence of apathy in PD of 39.8% (n = 5,388, 905% CI 34.6-45.0%). Apathy was associated with higher age (3.3 years, 95% CI = 1.7-4.9), lower mean Mini-Mental State Evaluation (MMSE) score (-1.4 points, 95% CI = -2.1 to -0.8), an increased risk of co-morbid depression (relative risk [RR] = 2.3, 95% CI = 1.9-2.8), higher Unified Parkinson's Disease Rating Scale (UPDRS) motor score (6.5 points, 95% CI = 2.6-10.3), and more severe disability (Hedges-G = 0.5, 95% CI = 0.3-0.6). Half of the patients with apathy had concomitant depression (57.2%, 95% CI = 49.4-64.9%), and this estimate was similar after exclusion of patients with cognitive impairment (52.5%, 95% CI = 42.2%-62.8%). In conclusion, we found that apathy affects almost 40% of patients with PD. Several factors influence reported prevalence rates, contributing to the considerable heterogeneity in study results. Half of patients with apathy do not suffer from concomitant depression or cognitive impairment, confirming its status as a separate clinical syndrome in PD. The pervasiveness of apathy in PD warrants research into its treatment, although different underlying pathophysiological mechanisms may require different treatment strategies. Treatment of apathy could improve patient quality of life, reduce caregiver burden, alleviate disability by increasing motivation for self-care, and reduce cognitive impairment by improving executive functioning.

10 Review Hypothesis: a role for EBV-induced molecular mimicry in Parkinson's disease. 2014

Woulfe, John M / Gray, Madison T / Gray, Douglas A / Munoz, David G / Middeldorp, Jaap M. ·Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada; Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada. Electronic address: jwoulfe@ottawahospital.on.ca. · Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada. · Department of Pathology, St. Michael's Hospital, Toronto, Canada. · Department of Pathology, VU Medical Center, Amsterdam, The Netherlands. ·Parkinsonism Relat Disord · Pubmed #24726430.

ABSTRACT: Current concepts regarding the pathogenesis of Parkinson's disease support a model whereby environmental factors conspire with a permissive genetic background to initiate the disease. The identity of the responsible environmental trigger has remained elusive. There is incontrovertible evidence that aggregation of the neuronal protein alpha-synuclein is central to disease pathogenesis. A novel hypothesis of Parkinson's pathogenesis, articulated by Braak and colleagues, implicates a pathogen acting in the olfactory mucosa and gastrointestinal tract as the inciting agent. In this point-of-view article, we hypothesize that α-synuclein aggregation in Parkinson's disease is an Epstein-Barr virus (EBV)-induced autoimmune phenomenon. Specifically, we have shown evidence for molecular mimicry between the C-terminal region of α-synuclein and a repeat region in the latent membrane protein 1 encoded by EBV. We hypothesize that, in genetically-susceptible individuals, anti-EBV latent membrane protein antibodies targeting the critical repeat region cross react with the homologous epitope on α-synuclein and induce its oligomerization. Consistent with the Braak's proposed pattern of spread, we contend that axon terminals in the lamina propria of the gut are among the initial targets, with subsequent spread of pathology to the CNS. While at this time, we can only provide evidence from the literature and preliminary findings from our own laboratory, we hope that our hypothesis will stimulate the development of tractable experimental systems that can be exploited to test it. Further support for an EBV-induced immune pathogenesis for Parkinson's disease could have profound therapeutic implications.

11 Review Parkinson's disease mild cognitive impairment: application and validation of the criteria. 2014

Geurtsen, Gert J / Hoogland, Jeroen / Goldman, Jennifer G / Schmand, Ben A / Tröster, Alexander I / Burn, David J / Litvan, Irene / Anonymous4010777. ·Department of Neurology, Academic Medical Center Amsterdam, The Netherlands. · Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. · Department of Neurology, Academic Medical Center Amsterdam, The Netherlands Department of Psychology, University of Amsterdam, The Netherlands. · Barrow Neurological Institute, Muhammad Ali Parkinson Center, Phoenix, AZ, USA. · Institute for Aging and Health, Newcastle University, Newcastle upon Tyne, UK. · Department of Neurosciences University of California, Movement Disorder Center, San Diego, CA, USA. ·J Parkinsons Dis · Pubmed #24296865.

ABSTRACT: Dementia in Parkinson's disease (PD) is a serious health issue and a major concern for many patients. In most cases mild cognitive impairment (MCI) is considered a transitional stage between normal cognitive functioning and dementia which is of potential importance in the early identification of patients at risk for dementia. Recently, the Movement Disorder Society (MDS) proposed diagnostic criteria for MCI in PD (PD-MCI). These criteria comprise two operationalizations: Level I (based on an abbreviated assessment) and Level II (based on comprehensive neuropsychological evaluation permitting MCI subtyping). These criteria need to be validated. This paper describes a project aiming to validate the MDS PD-MCI criteria by pooling and analyzing cross-sectional and longitudinal neuropsychological databases comprising ≥5,500 PD patients and ≥1,700 controls. After applying the MDS PD-MCI Level I and Level II criteria, rates of conversion to PD-dementia and predictive variables for conversion to PD-dementia will be established. This study will also assist in identifying whether revisions of the PD-MCI criteria are required.

12 Review The role of SPECT imaging of the dopaminergic system in translational research on Parkinson's disease. 2014

Suwijn, Sven R / de Bruin, Kora / de Bie, Rob M A / Booij, Jan. ·Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ·Parkinsonism Relat Disord · Pubmed #24262177.

ABSTRACT: Imaging of the dopaminergic system with single photon emission computed tomography (SPECT), and particularly of the dopamine transporter (DAT) located in the striatum, is a well accepted tool in clinical practice to confirm or exclude loss of nigrostriatal dopamine (DA) neurons in patients suspected to suffer from Parkinson's disease (PD). SPECT techniques were developed successfully to image neurotransmitter systems, including the presynaptic DAT and postsynaptic dopamine D2/3 receptors, in rat and mouse models of PD. Here we review the results of preclinical SPECT studies of the dopaminergic system in rat and mouse models of PD. Initially, SPECT studies in animal models of PD were performed to validate that micro-SPECT is able to accurately assess parts of the dopaminergic system in small animals in-vivo. However, more recently, micro-SPECT DAT is increasingly used as a research tool to support the interpretation of human DAT SPECT studies in PD, including clinical trials examining the effects of potential neuroprotective drugs. Translational research with SPECT is an interesting development which may further increase our understanding of the pathophysiology and treatment of PD.

13 Review Depression and impulse control disorders in Parkinson's disease: two sides of the same coin? 2014

Vriend, Chris / Pattij, Tommy / van der Werf, Ysbrand D / Voorn, Pieter / Booij, Jan / Rutten, Sonja / Berendse, Henk W / van den Heuvel, Odile A. ·Department of Psychiatry, VU University Medical Center (VUmc), Amsterdam, The Netherlands; Department of Anatomy & Neurosciences, VUmc, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU/VUmc, Amsterdam, The Netherlands. Electronic address: c.vriend@vumc.nl. · Department of Anatomy & Neurosciences, VUmc, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU/VUmc, Amsterdam, The Netherlands. · Department of Anatomy & Neurosciences, VUmc, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU/VUmc, Amsterdam, The Netherlands; Department of Emotion & Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. · Department of Anatomy & Neurosciences, VUmc, Amsterdam, The Netherlands. · Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. · Department of Psychiatry, VU University Medical Center (VUmc), Amsterdam, The Netherlands; Department of Anatomy & Neurosciences, VUmc, Amsterdam, The Netherlands. · Neuroscience Campus Amsterdam, VU/VUmc, Amsterdam, The Netherlands; Department of Neurology, VUmc, Amsterdam, The Netherlands. · Department of Psychiatry, VU University Medical Center (VUmc), Amsterdam, The Netherlands; Department of Anatomy & Neurosciences, VUmc, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU/VUmc, Amsterdam, The Netherlands. ·Neurosci Biobehav Rev · Pubmed #24239733.

ABSTRACT: Depression and impulse control disorders (ICD) are two common neuropsychiatric features in Parkinson's disease (PD). Studies have revealed that both phenomena are associated with aberrations in ventral striatal dopamine signaling and concomitant dysfunction of the reward-related (limbic) cortico-striatal-thalamocortical (CSTC) circuit. Depression in PD seems associated with decreased activity in the limbic CSTC circuit, whereas ICD seem associated with increased limbic CSTC circuit activity, usually after commencing dopamine replacement therapy (DRT). Not all DRT using PD patients, however, develop symptoms of ICD, suggesting an additional underlying neurobiological susceptibility. Furthermore, the symptoms of depression and ICD frequently coincide even though they are related to seemingly contrasting limbic CSTC circuit activation states. The aim of this review is to provide an overview of the currently available literature on the neurobiology of PD-related depression and ICD and discusses possible susceptibility factors. Finally, we propose a neurobiological model that identifies ventral striatal dopaminergic denervation as a common underlying neurobiological substrate of depression and ICD and subsequent dysfunction of reward and motivation-related brain areas.

14 Review Pharmacological treatment of dementia: a scoping review of systematic reviews. 2013

van de Glind, Esther M M / van Enst, Wynanda A / van Munster, Barbara C / Olde Rikkert, Marcel G M / Scheltens, Philip / Scholten, Rob J P M / Hooft, Lotty. ·Section of Geriatrics, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ·Dement Geriatr Cogn Disord · Pubmed #23941762.

ABSTRACT: BACKGROUND: Until now, multiple reviews on the pharmacological treatment of dementia have been published. METHODS: We performed a scoping review to summarize research findings and to identify gaps in the existing literature. We searched the literature and assessed the risk of bias of the included reviews. A team of clinical experts assessed the fields in which more research is necessary. Fifty-five reviews with a low risk of bias were included, most of them concerning the treatment of cognitive decline (n = 16) and behavioral symptoms (n = 10) in Alzheimer's disease (AD). For cognitive impairment, cholinesterase inhibitors (n = 13) and memantine (n = 7) were described most frequently. Little information was found about the treatment of depression in dementia. CONCLUSIONS: For many current treatments, there is sufficient evidence. New research should focus on the symptomatic treatment of the earliest and most salient complaints in AD as well as on disease-modifying interventions acting at the level of the amyloid cascade.

15 Review Resident adult neural stem cells in Parkinson's disease--the brain's own repair system? 2013

van den Berge, Simone A / van Strien, Miriam E / Hol, Elly M. ·Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands. ·Eur J Pharmacol · Pubmed #23872414.

ABSTRACT: One important pathological process in the brain of Parkinson disease (PD) patients is the degeneration of the dopaminergic neurons in the substantia nigra, which leads to a decline in striatal dopamine levels and motor dysfunction. A major clinical problem is that this degenerative process currently cannot be stopped or reversed. Expectations from the restorative capacity of neural stem cells (NSCs) are high, as these cells can potentially replace the degenerating neurons. The discovery of the presence of NSCs in the adult human brain has instigated research into the potential of these cells as a resource to promote brain repair in neurodegenerative diseases. Neural stem and progenitor cells reside in the subventricular zone (SVZ), which is closely situated to the striatum, which is affected in PD. Therefore, restoring the dopamine levels in the striatum of PD patients through stimulating endogenous NSCs in the nearby SVZ to migrate into the striatum and differentiate into dopaminergic neurons might thus be an attractive future therapeutic approach. We will review the reported changes in NSCs in the SVZ of PD animal models and PD patients, which are due to a lack of striatal dopamine. Furthermore, we will summarise the reports that describe efforts to stimulate NSCs to replace dopaminergic cells in the SN and restore striatal dopamine levels. In our opinion, mobilizing the endogenous SVZ NSCs to replenish striatal dopamine is an attractive approach to alleviate the motor symptoms in PD patients, without the ethical and immunological challenges of transplantation of NSCs and foetal brain tissue.

16 Review Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. 2012

del Campo, Marta / Mollenhauer, Brit / Bertolotto, Antonio / Engelborghs, Sebastiaan / Hampel, Harald / Simonsen, Anja Hviid / Kapaki, Elisabeth / Kruse, Niels / Le Bastard, Nathalie / Lehmann, Sylvain / Molinuevo, Jose L / Parnetti, Lucilla / Perret-Liaudet, Armand / Sáez-Valero, Javier / Saka, Esen / Urbani, Andrea / Vanmechelen, Eugeen / Verbeek, Marcel / Visser, Pieter Jelle / Teunissen, Charlotte. ·Department of Clinical Chemistry, Neurology Laboratory, VU University medical center, De Boelelaan 1117, Amsterdam, The Netherlands. m.delcampomilan@vumc.nl ·Biomark Med · Pubmed #22917144.

ABSTRACT: Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (α-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein. The proposed standardized operating procedures are applicable not only to novel CSF biomarkers in AD and PD, but also to biomarkers for other neurodegenerative disorders.

17 Review Emerging roles of microglial activation and non-motor symptoms in Parkinson's disease. 2012

Doorn, Karlijn J / Lucassen, Paul J / Boddeke, Hendrikus W / Prins, Marloes / Berendse, Henk W / Drukarch, Benjamin / van Dam, Anne-Marie. ·University of Amsterdam, Swammerdam Institute for Life Sciences, Center for Neuroscience, Amsterdam, The Netherlands. ·Prog Neurobiol · Pubmed #22732265.

ABSTRACT: Recent data has indicated that the traditional view of Parkinson's disease (PD) as an isolated disorder of the nigrostriatal dopaminergic system alone is an oversimplification of its complex symptomatology. Aside from classical motor deficits, various non-motor symptoms including autonomic dysfunction, sensory and cognitive impairments as well as neuropsychiatric alterations and sleep disturbances are common in PD. Some of these non-motor symptoms can even antedate the motor problems. Many of them are associated with extranigral neuropathological changes, such as extensive α-synuclein pathology and also neuroinflammatory responses in specific brain regions, i.e. microglial activation, which has been implicated in several aspects of PD pathogenesis and progression. However, microglia do not represent a uniform population, but comprise a diverse group of cells with brain region-specific phenotypes that can exert beneficial or detrimental effects, depending on the local phenotype and context. Understanding how microglia can be neuroprotective in one brain region, while promoting neurotoxicity in another, will improve our understanding of the role of microglia in neurodegeneration in general, and of their role in PD pathology in particular. Since neuroinflammatory responses are in principle modifiable, such approaches could help to identify new targets or adjunctive therapies for the full spectrum of PD-related symptoms.

18 Review Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson's disease. 2012

Ravid, Rivka / Ferrer, Isidro. ·Brain Bank Consultants, Amsterdam, The Netherlands. rivkagravid@gmail.com ·FEBS J · Pubmed #22313511.

ABSTRACT: Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson's disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field. We emphasize the potentials and pitfalls when using high-quality specimens of the human central nervous system for advancing PD research. PD is a generalized disease in which α-synuclein is not a unique component but, instead, is only one of the players accounting for the complex impairment of biochemical/molecular processes involved in metabolic pathways. This is particularly important in the cerebral cortex, where altered cognition has a complex neurochemical substrate. Mitochondria and energy metabolism impairment, abnormal RNA, microRNA, protein synthesis, post-translational protein modifications and alterations in the lipid composition of membranes and lipid rafts are part of these complementary factors. We have to be alert to the possible pitfalls of each specimen and its suitability for a particular study. Not all samples qualify for the study of DNA, RNA, proteins, post-translational modifications, lipids and metabolomes, although the use of carefully selected samples and appropriate methods minimizes pitfalls and errors and guarantees high-quality reserach.

19 Review Activation of the unfolded protein response is an early event in Alzheimer's and Parkinson's disease. 2012

Hoozemans, Jeroen J M / van Haastert, Elise S / Nijholt, Diana A T / Rozemuller, Annemieke J M / Scheper, Wiep. ·Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. ·Neurodegener Dis · Pubmed #22302012.

ABSTRACT: BACKGROUND: Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation and aggregation of misfolded proteins. Disturbed homeostasis in the endoplasmic reticulum leads to accumulation of misfolded proteins, which triggers a stress response called the unfolded protein response (UPR) that protects the cell against the toxic buildup of misfolded proteins. OBJECTIVE: In this paper, we will briefly review the early involvement of the UPR in the pathology of AD and PD. METHODS: Expression of UPR activation markers was analyzed in human brain tissue using immunohistochemistry and Western blot analysis. RESULTS: Neuropathological studies demonstrate that UPR activation markers are increased in neurons in AD and PD. In AD, UPR activation markers are observed in neurons with diffuse staining of phosphorylated tau protein. In PD, increased immunoreactivity for UPR activation markers is detected in neuromelanin containing dopaminergic neurons of the substantia nigra, which colocalize with diffuse α-synuclein staining. CONCLUSION: UPR activation is closely associated with the first stages of accumulation and aggregation of the toxic proteins involved in AD and PD. Studies of postmortem brain tissue indicate that UPR activation is an early event in neurodegeneration.

20 Review Patterns of α-synuclein pathology in incidental cases and clinical subtypes of Parkinson's disease. 2012

van de Berg, Wilma D J / Hepp, Dagmar H / Dijkstra, Anke A / Rozemuller, J Annemieke M / Berendse, Henk W / Foncke, E. ·Department of Anatomy and Neurostiences, Neurostience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. wdj.vandeberg@vumc.nl ·Parkinsonism Relat Disord · Pubmed #22166446.

ABSTRACT: Parkinson's disease (PD) is characterized by a gradual accumulation of neuropathology that may begin many years before a clinical diagnosis can be made using currently accepted criteria. Here, we first review the prevalence of α-synuclein neuropathology in elderly and discuss its clinical relevance in Parkinson patients. Subsequently, the results of a retrospective study focussing on the distribution of neuropathology in Parkinson patients with a tremor-dominant (TD), non-tremordominant (NTD) or rapid disease progression (RDP) subtype are presented. The study population recruited by the Netherlands Brain bank consisted of 149 non-neurological donors, 26 donors with incidental Lewy body disease (iLBD) and 111 Parkinson patients. In total, 89% of these cases could be classified in accordance with the Braak staging when taking into account the severity of α-synuclein pathology and adding an amygdala-predominant category of synucleinopathy. The pathological progression seemed to be non-linear. Interestingly, a strong correlation between neuronal loss and α-synuclein pathology was observed in the substantia nigra in Braak stages 3-6 (P < 0.01). However, there was no correlation between Hoehn & Yahr and Braak stages. Neuropathological progression may, however, vary between subtypes as cortical Lewy body load and Braak stages were higher in patients with NTD compared to TD and Alzheimer pathology was more prevalent in RDP patients. Recognition of clinical subtypes in neuropathological studies is essential to identify selective vulnerability to protein accumulation that may determine the clinical phenotype in PD.

21 Review Monitoring therapeutic effects in Parkinson's disease by serial imaging of the nigrostriatal dopaminergic pathway. 2011

Booij, Jan / Berendse, Henk W. ·Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. j.booij@amc.uva.nl ·J Neurol Sci · Pubmed #21840542.

ABSTRACT: PET and SPECT are very sensitive techniques to detect in-vivo nigrostriatal degeneration in Parkinson's disease, even in the pre-motor phase of the disease. Furthermore, these techniques are able to measure disease progression. However, caution must be used in the interpretation of studies in which therapeutic effects in Parkinson's disease were also monitored by serial imaging of nigrostriatal neurons, as disparity between imaging and clinical outcomes has been reported in several clinical studies.

22 Review Prevalence of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis. 2011

Velseboer, Daan C / de Haan, Rob J / Wieling, Wouter / Goldstein, David S / de Bie, Rob M A. ·Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands. ·Parkinsonism Relat Disord · Pubmed #21571570.

ABSTRACT: BACKGROUND: Although orthostatic hypotension (OH) is recognized as one of the main non-motor symptoms of Parkinson's disease (PD), there is inconsistent evidence about the prevalence of OH in PD. To estimate the prevalence of OH in PD more precisely we conducted a systematic review of the literature. METHODS: From PubMed and Embase searches with predefined inclusion criteria, we identified studies published up till December 2009. Prevalence numbers from studies were pooled using a non-linear random-effects meta-analysis. RESULTS: We found 25 studies from which the prevalence of OH could be calculated. The pooled estimate of the point prevalence of OH in PD was 30.1% (95% CI: 22.9% to 38.4%). We found a large statistical heterogeneity between studies which could not be reduced by several subgroup analyses. CONCLUSIONS: The estimated prevalence of OH in PD is 30%. However, due to the large heterogeneity between studies this pooled estimate should be interpreted with caution. More data from unselected population-based cohorts are needed.

23 Review Neurosteroid and GABA-A receptor alterations in Alzheimer's disease, Parkinson's disease and multiple sclerosis. 2011

Luchetti, S / Huitinga, I / Swaab, D F. ·Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. s.luchetti@nin.knaw.nl ·Neuroscience · Pubmed #21514366.

ABSTRACT: Steroid hormones (e.g. estrogens, androgens, progestagens) which are synthesized de novo or metabolized within the CNS are called neurosteroids. There is substantial evidence from animal studies suggesting that these steroids can affect brain function by modulating neurotransmission, and influence neuronal survival, neuronal and glial differentiation and myelination in the CNS by regulating gene expression of neurotrophic factors and anti-inflammatory molecules. Indeed, evidence is emerging that expression of the enzymes responsible for the synthesis of neurosteroids changes in neurodegenerative diseases. Some of these changes may contribute to the pathology, while others, conversely, may represent an attempted rescue program in the diseased brain. Here we review the data on changes in neurosteroid levels and neurosteroid synthesis pathways in the human brain in three neurodegenerative conditions, Alzheimers's (AD) and Parkinson's (PD) diseases and Multiple Sclerosis (MS) and the extent to which these findings may implicate protective or pathological roles for neurosteroids in the course of these diseases.Some neurosteroids can modulate neurotransmitter activity, for example, the pregnane steroids allopregnanolone and 3α5α-tetrahydro-deoxycorticosterone which are potent positive allosteric modulators of ionotropic GABA-A receptors. Therefore, neurosteroid-modulated GABA-A receptor subunit alterations found in AD and PD will also be discussed. These data imply an involvement of neurosteroid changes in the neurodegenerative and neuroinflammatory processes and suggest that they may deserve further investigation as potential therapeutic agents in AD, PD and MS. Finally, suggestions for therapeutic strategies will be included. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

24 Review [Impulse control disorders in Parkinson's disease]. 2011

Van den Heuvel, O A / Van der Werf, Y D / Groenewegen, H J / Foncke, E M J / Berendse, H W. ·Afdeling Psychiatrie, Psychiatrisch Consultatieve Dienst, VU Medisch Centrum, Amsterdam. oa.vandenheuvel@vumc.nl ·Tijdschr Psychiatr · Pubmed #21506077.

ABSTRACT: BACKGROUND: Parkinson's disease is characterised not only by the classic triad of bradykinesia, rigidity and tremor, but also by the frequent occurrence of various non-motor symptoms such as the impulse control disorders (pathological gambling, hypersexuality, compulsive buying, binge eating, punding and dopamine dependency). AIM: To increase insight into the clinical presentation, risk factors, treatment and the underlying pathophysiological mechanisms of impulse control disorders in Parkinson's disease. METHOD: Relevant literature was reviewed. RESULTS: Impulse control disorders belong to an important group of neuropsychiatric disorders that occur at some point in 5-10% of patients with Parkinson's disease. They generally occur in conjunction with dopaminergic medication and can have a marked social, relational and/ or financial impact. CONCLUSION: Early recognition of impulse control disorders in Parkinson's disease is important and a close collaboration between the neurologist and the psychiatrist is essential in order to ensure correct diagnosis and the best possible treatment. Impulse control disorders in Parkinson's disease show considerable phenomenological overlap with other repetitive behaviours within the impulsive-compulsive spectrum of disorders to which the obsessive-compulsive disorders and addiction disorders belong. The overlap can possibly be explained by a shared pathophysiological mechanism involving an imbalance between the direct and indirect pathways of the dorsal and ventral frontal-striatal circuits.

25 Review Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: a pathogenetically based approach. 2010

van Dijk, Karin D / Teunissen, Charlotte E / Drukarch, Benjamin / Jimenez, Connie R / Groenewegen, Henk J / Berendse, Henk W / van de Berg, Wilma D J. ·Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. Karin.vanDijk@vumc.nl ·Neurobiol Dis · Pubmed #20451609.

ABSTRACT: The inaccuracy of the early diagnosis of Parkinson's disease (PD) has been a major incentive for studies aimed at the identification of biomarkers. Brain-derived cerebrospinal fluid (CSF) proteins are potential biomarkers considering the major role that proteins play in PD pathogenesis. In this review, we discuss the current hypotheses about the pathogenesis of PD and identify the most promising candidate biomarkers among the CSF proteins studied so far. The list of potential markers includes proteins involved in various pathogenetic processes, such as oxidative stress and protein aggregation. This list will undoubtedly grow in the near future by application of CSF proteomics and subsequent validation of identified proteins. Probably a single biomarker will not suffice to reach high sensitivity and specificity, because PD is pathogenetically heterogeneous and shares etiological factors with other neurodegenerative diseases. Furthermore, identified candidate biomarkers will have to be thoroughly validated before they can be implemented as diagnostic aids.

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