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Parkinson's Foundation

Gioele La Manno, Daniel Gyllborg, Simone Codeluppi, Kaneyasu Nishimura, Carmen Salto, Amit Zeisel, Lars E Borm, Simon R W Stott, Enrique M Toledo, J Carlos Villaescusa, Peter Lönnerberg, Jesper Ryge, Roger A Barker, Ernest Arenas, Sten Linnarsson
Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like cells and four progenitors. In the mouse, two mature fetal dopaminergic neuron subtypes diversified into five adult classes during postnatal development...
October 6, 2016: Cell
Joanne Trinh, Emil K Gustavsson, Carles Vilariño-Güell, Stephanie Bortnick, Jeanne Latourelle, Marna B McKenzie, Chelsea Szu Tu, Ekaterina Nosova, Jaskaran Khinda, Austen Milnerwood, Suzanne Lesage, Alexis Brice, Meriem Tazir, Jan O Aasly, Laura Parkkinen, Hazal Haytural, Tatiana Foroud, Richard H Myers, Samia Ben Sassi, Emna Hentati, Fatma Nabli, Emna Farhat, Rim Amouri, Fayçal Hentati, Matthew J Farrer
BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13-30% in Ashkenazi Jewish populations, and 30-40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others remain asymptomatic despite advanced age. We aimed to use a genome-wide approach to identify genetic variability that directly affects LRRK2 Gly2019Ser penetrance...
November 2016: Lancet Neurology
Annette Hand, William K Gray, Lloyd L Oates, Megan Woolford, Anna Todd, Elizabeth Bale, Catherine Jones, Brian H Wood, Richard W Walker
BACKGROUND: People with Parkinson's disease (PD) and parkinsonism living in care homes (residential or nursing care) in the UK represent around 10-15% of all people with PD and 3-5% of all care home residents. There are few previous data on medication use in those living in care homes with PD. In this study we aimed to compare medication use in a representative cohort of people with PD living in care homes in north-east England with those living in their own homes. METHOD: All people with late stage (Hoehn and Yahr III-V) idiopathic PD, PD dementia, or atypical parkinsonian syndromes under the care of the Northumbria Healthcare NHS Foundation Trust PD service on 1st January 2015 were identified...
September 2, 2016: Parkinsonism & related Disorders
Sherrilene Classen, Jeffrey D Holmes, Liliana Alvarez, Katherine Loew, Ashley Mulvagh, Kayla Rienas, Victoria Walton, Wenqing He
Parkinson's disease (PD) is a neurodegenerative disorder that affects fitness to drive. Research that has examined clinical predictors of fitness to drive in PD, using the on-road assessment as the gold standard, has generally used a dichotomous pass/fail decision. However, on-road assessments may also result in one of two additional outcomes (pass with recommendations, or fail-remediable). Individuals within these subgroups may benefit from interventions to improve their fitness to drive abilities. This study investigated clinical predictors that could be indicative of the pass, pass with recommendations, or fail-remediable categories for drivers with PD (N = 99)...
October 2015: OTJR: Occupation, Participation and Health
Bai Li, Xi He, Yan Sun, Baixiang Li
Paraquat and maneb are identified environmental pollutants. Combined exposure to paraquat and maneb is a latent risk factor for many diseases, particularly those of the central nervous system, including Parkinson's disease and Alzheimer's disease. Hippocampus is the key structure in memory formation and babies are more sensitive to environmental stimuli than adults, so we investigated the neurotoxicity of paraquat and maneb on the hippocampi of rat pups. Female and male Sprague-Dawley rats were mated (female : male = 2 : 1) every night for a week...
October 20, 2016: Molecular BioSystems
Francesca Boscia, Gulnaz Begum, Giuseppe Pignataro, Rossana Sirabella, Ornella Cuomo, Antonella Casamassa, Dandan Sun, Lucio Annunziato
Sodium dynamics are essential for regulating functional processes in glial cells. Indeed, glial Na(+) signaling influences and regulates important glial activities, and plays a role in neuron-glia interaction under physiological conditions or in response to injury of the central nervous system (CNS). Emerging studies indicate that Na(+) pumps and Na(+) -dependent ion transporters in astrocytes, microglia, and oligodendrocytes regulate Na(+) homeostasis and play a fundamental role in modulating glial activities in neurological diseases...
October 2016: Glia
Nabila Dahodwala, Qinglin Pei, Peter Schmidt
OBJECTIVE: To describe characteristics of Parkinson's disease by sex and determine if differences in disease progression exist. DESIGN: Longitudinal, observational study. SETTING: Twenty-one National Parkinson Foundation Centers of Excellence. PARTICIPANTS: People (N = 4,679; 63% men and 37% women) with idiopathic Parkinson's disease. METHODS: Demographic and clinical data at enrollment and after 1 year were collected...
September 2016: Journal of Obstetric, Gynecologic, and Neonatal Nursing: JOGNN
Gustaf Edgren, Henrik Hjalgrim, Klaus Rostgaard, Paul Lambert, Agneta Wikman, Rut Norda, Kjell-Einar Titlestad, Christian Erikstrup, Henrik Ullum, Mads Melbye, Michael P Busch, Olof Nyrén
BACKGROUND: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health implications. OBJECTIVE: To investigate possible transfusion transmission of neurodegenerative disorders. DESIGN: Retrospective cohort study. SETTING: Nationwide registers of transfusions in Sweden and Denmark...
September 6, 2016: Annals of Internal Medicine
Douglas A Grow, DeNard V Simmons, Jorge A Gomez, Matthew J Wanat, John R McCarrey, Carlos A Paladini, Christopher S Navara
UNLABELLED: : The progressive death of dopamine producing neurons in the substantia nigra pars compacta is the principal cause of symptoms of Parkinson's disease (PD). Stem cells have potential therapeutic use in replacing these cells and restoring function. To facilitate development of this approach, we sought to establish a preclinical model based on a large nonhuman primate for testing the efficacy and safety of stem cell-based transplantation. To this end, we differentiated baboon fibroblast-derived induced pluripotent stem cells (biPSCs) into dopaminergic neurons with the application of specific morphogens and growth factors...
September 2016: Stem Cells Translational Medicine
Jori E Fleisher, Krunal Shah, Whitney Fitts, Nabila A Dahodwala
BACKGROUND: Low health literacy (HL) indicates a limited ability to understand and use basic information to make appropriate healthcare decisions. While low HL is associated with higher morbidity, mortality, and healthcare costs in multiple chronic conditions, little is known about HL and its associations in Parkinson's disease (PD). METHODS: Cross-sectional study of non-demented adults with PD participating in the National Parkinson Foundation Parkinson's Outcomes Project at the University of Pennsylvania...
May 2016: Movement Disorders Clinical Practice
Joseph H Friedman, James C Beck, Kelvin L Chou, Gracia Clark, Christopher P Fagundes, Christopher G Goetz, Karen Herlofson, Benzi Kluger, Lauren B Krupp, Anthony E Lang, Jao-Shin Lou, Laura Marsh, Anne Newbould, Daniel Weintraub
Fatigue is a severe problem for many people living with Parkinson's disease (PD). Best estimates suggest that more than 50% of patients experience this debilitating symptom. Little is known about its etiology or treatment, making the understanding of fatigue a true unmet need. As part of the Parkinson's Disease Foundation Community Choice Research Program, patients, caregivers, and scientists attended a symposium on fatigue on 16 and 17 October 2014. We present a summary of that meeting, reviewing what is known about the diagnosis and treatment of fatigue, its physiology, and what we might learn from multiple sclerosis (MS), depression, and cancer-disorders in which fatigue figures prominently too...
2016: NPJ Parkinsons Dis
Richard Grondin, Yi Ai, Peter A Hardy, Mark T Butt, Brian D Nelson, Jack D Lemmon, David Bumcrot, Don M Gash, Greg A Gerhardt, Zhiming Zhang
OBJECTIVE A better understanding of the effects of chronically delivering compounds to the substantia nigra and nearby areas is important for the development of new therapeutic approaches to treat alpha-synucleinopathies, like Parkinson's disease. Whether chronic intranigral delivery of an infusate could be achieved without causing motor dysfunction or marked pathology remains unclear. The authors evaluated the tolerability of continuously delivering an infusate directly into the rhesus monkey substantia nigra via a programmable pump coupled to a novel intraparenchymal needle-tip catheter surgically implanted using MRI-guided techniques...
May 27, 2016: Journal of Neurosurgery
Un Jung Kang, Jennifer G Goldman, Roy N Alcalay, Tao Xie, Paul Tuite, Claire Henchcliffe, Penelope Hogarth, Amy W Amara, Samuel Frank, Alice Rudolph, Cynthia Casaceli, Howard Andrews, Katrina Gwinn, Margaret Sutherland, Catherine Kopil, Lona Vincent, Mark Frasier
BACKGROUND: Identifying PD-specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well-characterized, clinically typical, moderate to advanced PD cohorts is critically needed. METHODS: BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross-sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects...
June 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Yue Pei, Aman Asif-Malik, Juan J Canales
Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the "classical" biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA), norepinephrine, epinephrine, serotonin (5-HT), and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS), and hence referred to as "trace" amines (TAs), are now recognized to play significant neurophysiological and behavioral functions...
2016: Frontiers in Neuroscience
Kayla R Donaldson, Belel Ait Oumeziane, Sebastien Hélie, Dan Foti
Adapting behavior to dynamic stimulus-reward contingences is a core feature of reversal learning and a capacity thought to be critical to socio-emotional behavior. Impairment in reversal learning has been linked to multiple psychiatric outcomes, including depression, Parkinson's disorder, and substance abuse. A recent influential study introduced an innovative laboratory reversal-learning paradigm capable of disentangling the roles of feedback valence and expectancy. Here, we sought to use this paradigm in order to examine the time-course of reward and punishment learning using event-related potentials among a large, representative sample (N=101)...
July 1, 2016: Physiology & Behavior
Dolores Vilas, Leslie M Shaw, Peggy Taylor, Daniela Berg, Kathrin Brockmann, Jan Aasly, Connie Marras, Claustre Pont-Sunyer, José Ríos, Ken Marek, Eduardo Tolosa
BACKGROUND: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of inherited Parkinson's disease (PD). Nonmanifesting carriers of LRRK2 mutations are at high risk for developing PD. Information available on cerebrospinal fluid (CSF) biomarkers in LRRK2 carriers remains preliminary. OBJECTIVES: To measure CSF levels of α-synuclein, β amyloid1-42 , total-tau, and phospho-tau181 , in LRRK2-associated PD, idiopathic PD, nonmanifesting carriers, and first-degree relatives of LRRK2-associated PD patients without the mutation (nonmanifesting noncarriers)...
June 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Kin Y Mok, Una Sheerin, Javier Simón-Sánchez, Afnan Salaka, Lucy Chester, Valentina Escott-Price, Kiran Mantripragada, Karen M Doherty, Alastair J Noyce, Niccolo E Mencacci, Steven J Lubbe, Caroline H Williams-Gray, Roger A Barker, Karin D van Dijk, Henk W Berendse, Peter Heutink, Jean-Christophe Corvol, Florence Cormier, Suzanne Lesage, Alexis Brice, Kathrin Brockmann, Claudia Schulte, Thomas Gasser, Thomas Foltynie, Patricia Limousin, Karen E Morrison, Carl E Clarke, Stephen Sawcer, Tom T Warner, Andrew J Lees, Huw R Morris, Mike A Nalls, Andrew B Singleton, John Hardy, Andrey Y Abramov, Vincent Plagnol, Nigel M Williams, Nicholas W Wood
BACKGROUND: Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. METHODS: We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11...
May 2016: Lancet Neurology
Roger A Barker, Malin Parmar, Agnete Kirkeby, Anders Björklund, Lachlan Thompson, Patrik Brundin
Recent news of an impending clinical cell transplantation trial in Parkinson's disease using parthenogenetic stem cells as a source of donor tissue have raised hopes in the patient community and sparked discussion in the research community. Based on discussions held by a global collaborative initiative on translation of stem cell therapy in Parkinson's disease, we have identified a set of key questions that we believe should be addressed ahead of every clinical stem cell-based transplantation trial in this disorder...
2016: Journal of Parkinson's Disease
Hyung Ho Yoon, Joongkee Min, Eunmi Hwang, C Justin Lee, Jun-Kyo Francis Suh, Onyou Hwang, Sang Ryong Jeon
BACKGROUND: The inhibition of neuronal activity by electrical deep brain stimulation is one of the mechanisms explaining the amelioration of levodopa-induced dyskinesia. However, electrical deep brain stimulation cannot specifically activate or inactivate selected types of neurons. OBJECTIVES: We applied optogenetics as an alternative treatment to deep brain stimulation for levodopa-induced dyskinesia, and also to confirm that the mechanism of levodopa-induced dyskinesia amelioration by subthalamic nucleus deep brain stimulation is mediated through neuronal inhibition...
2016: Stereotactic and Functional Neurosurgery
Julie Penfold
No abstract text is available yet for this article.
February 2016: Nursing Older People
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