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NPJ Parkinson's Disease

Stephanie Martin, Iñaki Iturrate, Ricardo Chavarriaga, Robert Leeb, Aleksander Sobolewski, Andrew M Li, Julien Zaldivar, Iulia Peciu-Florianu, Etienne Pralong, Mayte Castro-Jiménez, David Benninger, François Vingerhoets, Robert T Knight, Jocelyne Bloch, José Del R Millán
Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson's Disease (PD) motor symptoms. However, previous works have been inconsistent regarding the functional role of beta activity in untreated Parkinsonian states, questioning such role. We hypothesized that this inconsistency is due to the influence of electrophysiological broadband activity -a neurophysiological indicator of synaptic excitation/inhibition ratio- that could confound measurements of beta activity in STN recordings...
2018: NPJ Parkinson's Disease
Nataliya Titova, Oleg Levin, Elena Katunina, K Ray Chaudhuri
'Levodopa Phobia' is under-recognised in Parkinson's disease but can cause profound detrimental clinical complications if left to continue. Several types can be encountered in clinical practice and can be driven by a misplaced fear of levodopa-induced dyskinesias, other gastrointestinal side effects and also the theoretical notion that levodopa may be toxic to dopaminergic neurons in the brain. The condition can be underpinned by a sense of strong influence from the physicians or carers who are unwilling to prescribe or consider levodopa, and also high levels of anxiety or even impulsive compulsive traits in patients who have been influenced by available literature or social media-based information...
2018: NPJ Parkinson's Disease
L Anselmi, C Bove, F H Coleman, K Le, M P Subramanian, K Venkiteswaran, T Subramanian, R A Travagli
Increasing evidence suggests that environmental neurotoxicants or misfolded α-synuclein generated by such neurotoxicants are transported from the gastrointestinal tract to the central nervous system via the vagus nerve, triggering degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and causing Parkinson's disease (PD). We tested the hypothesis that gastric co-administration of subthreshold doses of lectins and paraquat can recreate the pathology and behavioral manifestations of PD in rats...
2018: NPJ Parkinson's Disease
Robert A Hauser
No abstract text is available yet for this article.
2018: NPJ Parkinson's Disease
Na Feng, Scott Simanski, Kazi Islam, Linda S Hynan, Thomas Kodadek, Dwight C German
Parkinson disease (PD) is a progressive neurodegenerative disease with motor symptoms that result from degeneration of midbrain dopaminergic neurons. Biomarker research seeks to identify the disease during the pre-symptomatic phase, which is a time when therapeutic intervention will be most helpful. Previously, we screened a combinatorial peptoid library to search for antibodies that are present at much higher levels in the serum of PD patients than in control subjects. One such compound, called the PD2 peptoid, was 84% accurate for the identification of de novo PD when employed as the capture agent in an enzyme-linked immunosorbent assay...
2018: NPJ Parkinson's Disease
Stefano Cataldi, Jordan Follett, Jesse D Fox, Igor Tatarnikov, Chelsie Kadgien, Emil K Gustavsson, Jaskaran Khinda, Austen J Milnerwood, Matthew J Farrer
Vacuolar protein sorting 35 (VPS35) is a core component of the retromer trimer required for endosomal membrane-associated protein trafficking. The discovery of a missense mutation, Vps35 p.D620N implicates retromer dysfunction in the pathogenesis of Parkinson's disease (PD). We have characterized a knock-in mouse with a Vps35 p.D620N substitution (hereafter referred to as VKI) at 3 months of age. Standardized behavioral testing did not observe overt movement disorder. Tyrosine hydroxylase (TH)-positive nigral neuron counts and terminal expression in striata were comparable across genotypes...
2018: NPJ Parkinson's Disease
Taylor Chomiak, Alexander Watts, Jacqueline Burt, Richard Camicioli, Sun Nee Tan, Martin J McKeown, Bin Hu
In Parkinson's disease (PD), concurrent declines in cognitive and motor domain function can severely limit an individual's ability to conduct daily tasks. Current diagnostic methods, however, lack precision in differentiating domain-specific contributions of cognitive or motor impairments based on a patients' clinical manifestation. Fear of falling (FOF) is a common clinical manifestation among the elderly, in which both cognitive and motor impairments can lead to significant barriers to a patients' physical and social activities...
2018: NPJ Parkinson's Disease
Diptaman Chatterjee, Mansi Bhatt, David Butler, Erwin De Genst, Christopher M Dobson, Anne Messer, Jeffrey H Kordower
Therapeutics designed to target α-synuclein (α-syn) aggregation may be critical in halting the progression of pathology in Parkinson's disease (PD) patients. Nanobodies are single-domain antibody fragments that bind with antibody specificity, but allow readier genetic engineering and delivery. When expressed intracellularly as intrabodies, anti-α-syn nanobodies fused to a proteasome-targeting proline, aspartate or glutamate, serine, and threonine (PEST) motif can modulate monomeric concentrations of target proteins...
2018: NPJ Parkinson's Disease
Katharine M von Herrmann, Lucas A Salas, Eileen M Martinez, Alison L Young, Joseph M Howard, Mary S Feldman, Brock C Christensen, Owen M Wilkins, Stephen L Lee, William F Hickey, Matthew C Havrda
Neuroinflammation is a well-characterized pathophysiology occurring in association with the progression of Parkinson's disease. Characterizing the cellular and molecular basis of neuroinflammation is critical to understanding its impact on the incidence and progression of PD and other neurologic disorders. Inflammasomes are intracellular pro-inflammatory pattern-recognition receptors capable of initiating and propagating inflammation. These cellular complexes are well characterized in the innate immune system and activity of the NLRP3 inflammasome has been reported in microglia...
2018: NPJ Parkinson's Disease
Erica J Melief, Jonathan W McKinley, Jonathan Y Lam, Nicole M Whiteley, Alec W Gibson, John F Neumaier, Charles W Henschen, Richard D Palmiter, Nigel S Bamford, Martin Darvas
Parkinson's disease (PD) is primarily associated with the degeneration of midbrain dopamine neurons, but it is now appreciated that pathological processes like Lewy-body inclusions and cell loss affect several other brain regions, including the central lateral (CL) and centromedian/parafascicular (CM/PF) thalamic regions. These thalamic glutamatergic neurons provide a non-cortical excitatory input to the dorsal striatum, a major projection field of dopamine neurons. To determine how thalamostriatal signaling may contribute to cognitive and motor abnormalities found in PD, we used a viral vector approach to generate mice with loss of thalamostriatal glutamate signaling specifically restricted to the dorsal striatum (CAV2Cre - Slc17a6 lox/lox mice)...
2018: NPJ Parkinson's Disease
Jeanette M Metzger, Colleen F Moore, Carissa A Boettcher, Kevin G Brunner, Rachel A Fleddermann, Helen N Matsoff, Henry A Resnikoff, Viktoriya Bondarenko, Timothy J Kamp, Timothy A Hacker, Todd E Barnhart, Patrick J Lao, Bradley T Christian, R Jerry Nickles, Catherine L Gallagher, James E Holden, Marina E Emborg
Loss of cardiac postganglionic sympathetic innervation is a characteristic pathology of Parkinson's disease (PD). It progresses over time independently of motor symptoms and is not responsive to typical anti-parkinsonian therapies. Cardiac sympathetic neurodegeneration can be mimicked in animals using systemic dosing of the neurotoxin 6-hydroxydopamine (6-OHDA). As in PD, 6-OHDA-induced neuronal loss is associated with increased inflammation and oxidative stress. To assess the feasibility of detecting changes over time in cardiac catecholaminergic innervation, inflammation, and oxidative stress, myocardial positron emission tomography with the radioligands [11 C] meta -hydroxyephedrine (MHED), [11 C]PBR28 (PBR28), and [61 Cu]diacetyl- bis ( N (4))-methylthiosemicarbazone (ATSM) was performed in 6-OHDA-intoxicated adult, male rhesus macaques ( n  = 10; 50 mg/kg i...
2018: NPJ Parkinson's Disease
C Marras, J C Beck, J H Bower, E Roberts, B Ritz, G W Ross, R D Abbott, R Savica, S K Van Den Eeden, A W Willis, C M Tanner
Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1)...
2018: NPJ Parkinson's Disease
Pablo Martinez-Martin, Jaime Kulisevsky, Pablo Mir, Eduardo Tolosa, Pilar García-Delgado, María-Rosario Luquin
Early clinical diagnosis of advanced Parkinson's disease (APD) may be difficult. This study aimed to validate a simple screening tool, the CDEPA questionnaire ("Cuestionario De Enfermedad de Parkinson Avanzada" [Questionnaire for Advanced Parkinson's Disease]), for the identification of APD in daily practice. The study included 173 consecutively selected patients with PD (40% were women, mean age was 68.4 ± 10.5 years), stratified according to the Hoehn and Yahr (HY) scale. The CDEPA questionnaire defined APD as the presence of severe disability requiring help for activities of daily living (ADL), motor fluctuations with limitation or inability to perform ADL, severe dysphagia, recurrent falls, or dementia...
2018: NPJ Parkinson's Disease
Jennifer G Goldman, Beth A Vernaleo, Richard Camicioli, Nabila Dahodwala, Roseanne D Dobkin, Terry Ellis, James E Galvin, Connie Marras, Jerri Edwards, Julie Fields, Robyn Golden, Jason Karlawish, Bonnie Levin, Lisa Shulman, Glenn Smith, Christine Tangney, Cathi A Thomas, Alexander I Tröster, Ergun Y Uc, Noreen Coyan, Crystal Ellman, Mike Ellman, Charlie Hoffman, Susan Hoffman, Don Simmonds
People with Parkinson's disease (PD) and their care partners frequently report cognitive decline as one of their greatest concerns. Mild cognitive impairment affects approximately 20-50% of people with PD, and longitudinal studies reveal dementia in up to 80% of PD. Through the Parkinson's Disease Foundation Community Choice Research Award Program, the PD community identified maintaining cognitive function as one of their major unmet needs. In response, a working group of experts across multiple disciplines was organized to evaluate the unmet needs, current challenges, and future opportunities related to cognitive impairment in PD...
2018: NPJ Parkinson's Disease
Faria Zafar, Ruksana Azhu Valappil, Sam Kim, Krisztina K Johansen, Anne Lynn S Chang, James W Tetrud, Peggy S Eis, Eli Hatchwell, J William Langston, Dennis W Dickson, Birgitt Schüle
The "Iowa kindred," a large Iowan family with autosomal-dominant Parkinson's disease, has been followed clinically since the 1920s at the Mayo Clinic. In 2003, the genetic cause was determined to be a 1.7 Mb triplication of the alpha-synuclein genomic locus. Affected individuals present with an early-onset, severe parkinsonism-dementia syndrome. Here, we present a descendant of the Iowa kindred with novel, disease-associated non-motor findings of reduced heart rate variability, complete anosmia, and a rare skin condition called colloid milium...
2018: NPJ Parkinson's Disease
Fabio A Zucca, Renzo Vanna, Francesca A Cupaioli, Chiara Bellei, Antonella De Palma, Dario Di Silvestre, Pierluigi Mauri, Sara Grassi, Alessandro Prinetti, Luigi Casella, David Sulzer, Luigi Zecca
During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson's disease. We have investigated protein and lipid systems involved in the formation of these organelles and in the synthesis of the neuromelanin of human substantia nigra. Membrane and matrix proteins characteristic of lysosomes were found in neuromelanin-containing organelles at a lower number than in typical lysosomes, indicating a reduced enzymatic activity and likely impaired capacity for lysosomal and autophagosomal fusion...
2018: NPJ Parkinson's Disease
Amy K Reeve, John P Grady, Eve M Cosgrave, Emma Bennison, Chun Chen, Philippa D Hepplewhite, Christopher M Morris
Mitochondrial dysfunction within the cell bodies of substantia nigra neurons is prominent in both ageing and Parkinson's disease. The loss of dopaminergic substantia nigra neurons in Parkinson's disease is associated with loss of synapses within the striatum, and this may precede neuronal loss. We investigated whether mitochondrial changes previously reported within substantia nigra neurons were also seen within the synapses and axons of these neurons. Using high resolution quantitative fluorescence immunohistochemistry we determined mitochondrial density within remaining dopaminergic axons and synapses, and quantified deficiencies of mitochondrial Complex I and Complex IV in these compartments...
2018: NPJ Parkinson's Disease
Siddharth Kharkar, Jonathan Richard Ellenbogen, Michael Samuel, Alexandra Rizos, Monty Silverdale, K Ray Chaudhuri, Keyoumars Ashkan
INTRODUCTION: Deep brain stimulation (DBS) markedly improves motor function in advanced Parkinson's disease (PD), but its effect on sleep is less clear. PATIENTS AND METHODS: Forty PD patients who had subthalamic DBS (STN-DBS) were identified from an on-going non-motor naturalistic longitudinal study (NILS). All patients were followed up for at least 6 months, 26 patients had a 1 year follow-up. A total PDSS score of 100 or less, a score in any PDSS-item of 6 or less, and a Epworth score of 10 or more were classified as being significant...
2018: NPJ Parkinson's Disease
Courtney C Walton, Loren Mowszowski, Moran Gilat, Julie M Hall, Claire O'Callaghan, Alana J Muller, Matthew Georgiades, Jennifer Y Y Szeto, Kaylena A Ehgoetz Martens, James M Shine, Sharon L Naismith, Simon J G Lewis
The pathophysiological mechanism of freezing of gait (FoG) has been linked to executive dysfunction. Cognitive training (CT) is a non-pharmacological intervention which has been shown to improve executive functioning in Parkinson's disease (PD). This study aimed to explore whether targeted CT can reduce the severity of FoG in PD. Patients with PD who self-reported FoG and were free from dementia were randomly allocated to receive either a CT intervention or an active control. Both groups were clinician-facilitated and conducted twice-weekly for seven weeks...
2018: NPJ Parkinson's Disease
Per Odin, K Ray Chaudhuri, Jens Volkmann, Angelo Antonini, Alexander Storch, Espen Dietrichs, Zvezdan Pirtošek, Tove Henriksen, Malcolm Horne, David Devos, Filip Bergquist
Motor aspects of Parkinson's disease, such as fluctuations and dyskinesia, can be reliably evaluated using a variety of "wearable" technologies, but practical guidance on objective measurement (OM) and the optimum use of these devices is lacking. Therefore, as a first step, a panel of movement disorder specialists met to provide guidance on how OM could be assessed and incorporated into clinical guidelines. A key aspect of the incorporation of OM into the management of Parkinson's disease (PD) is defining cutoff values that separate "controlled" from "uncontrolled" symptoms that can be modified by therapy and that relate to an outcome that is relevant to the person with PD (such as quality of life)...
2018: NPJ Parkinson's Disease
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