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dementia with lewy bodies and Parkinson's

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https://www.readbyqxmd.com/read/28912672/maximizing-the-potential-of-longitudinal-cohorts-for-research-in-neurodegenerative-diseases-a-community-perspective
#1
Catherine J Moody, Derick Mitchell, Grace Kiser, Dag Aarsland, Daniela Berg, Carol Brayne, Alberto Costa, Mohammad A Ikram, Gail Mountain, Jonathan D Rohrer, Charlotte E Teunissen, Leonard H van den Berg, Joanna M Wardlaw
Despite a wealth of activity across the globe in the area of longitudinal population cohorts, surprisingly little information is available on the natural biomedical history of a number of age-related neurodegenerative diseases (ND), and the scope for intervention studies based on these cohorts is only just beginning to be explored. The Joint Programming Initiative on Neurodegenerative Disease Research (JPND) recently developed a novel funding mechanism to rapidly mobilize scientists to address these issues from a broad, international community perspective...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28911198/loss-of-native-%C3%AE-synuclein-multimerization-by-strategically-mutating-its-amphipathic-helix-causes-abnormal-vesicle-interactions-in-neuronal-cells
#2
Ulf Dettmer, Nagendran Ramalingam, Victoria E von Saucken, Tae-Eun Kim, Andrew J Newman, Elizabeth Terry-Kantor, Silke Nuber, Maria Ericsson, Saranna Fanning, Tim Bartels, Susan Lindquist, Oren A Levy, Dennis Selkoe
α-Synuclein (αS) forms round cytoplasmic inclusions in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Evidence suggests a physiological function of αS in vesicle trafficking and release. In contrast to earlier tenets, recent work indicates that αS normally exists in cells in a dynamic equilibrium between monomers and tetramers/multimers. We engineered αS mutants incapable of multimerization, leading to excess monomers at vesicle membranes. By EM, such mutants induced prominent vesicle clustering, leading to round cytoplasmic inclusions...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28904388/protective-efficacy-of-phosphodiesterase-1-inhibition-against-alpha-synuclein-toxicity-revealed-by-compound-screening-in-luhmes-cells
#3
Matthias Höllerhage, Claudia Moebius, Johannes Melms, Wei-Hua Chiu, Joachim N Goebel, Tasnim Chakroun, Thomas Koeglsperger, Wolfgang H Oertel, Thomas W Rösler, Marc Bickle, Günter U Höglinger
α-synuclein-induced neurotoxicity is a core pathogenic event in neurodegenerative synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. There is currently no disease-modifying therapy available for these diseases. We screened 1,600 FDA-approved drugs for their efficacy to protect LUHMES cells from degeneration induced by wild-type α-synuclein and identified dipyridamole, a non-selective phosphodiesterase inhibitor, as top hit. Systematic analysis of other phosphodiesterase inhibitors identified a specific phosphodiesterase 1 inhibitor as most potent to rescue from α-synuclein toxicity...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899330/rem-sleep-behaviour-disorder-not-just-a-bad-dream
#4
Elie Matar, Simon Jg Lewis
Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of the normal atonia during the REM stage of sleep, resulting in overt motor behaviours that usually represent the enactment of dreams. Patients will seek medical attention due to sleep-related injuries or unpleasant dream content. Idiopathic RBD which occurs independently of any other disease occurs in up to 2% of the older population. Meanwhile, secondary RBD is very common in association with certain neurodegenerative conditions...
September 18, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28890381/the-link-between-parkinson-s-disease-and-rapid-eye-movement-sleep-behavior-disorder-with-dream-enactment-possible-implications-for-early-rehabilitation
#5
Brian P Johnson, Kelly P Westlake
The purpose of this paper is twofold. First, to inform readers of the link between the loss of motor inhibition during rapid eye movement (REM) sleep dreaming, diagnosed as REM sleep behavior disorder (RBD), and the future onset of neurodegenerative disorders, such as Parkinson's Disease and dementia with lewy bodies. It has been reported that motor disinhibition during rapid eye movement sleep often precedes onset of these disorders by years or even decades. Second, to consider that identification of RBD and the early involvement of rehabilitation and/or development of home exercise plans may aid in prolonging and even increasing function, independence, and quality of life should such neurodegenerative disorders develop later in life...
September 7, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28879902/review-of-tremor-in-parkinson-s-disease-and-atypical-parkinsonian-disorders
#6
Pooja Mailankody, M Netravathi, Pramod Kumar Pal
Rest tremor (RT), a cardinal feature of Parkinson's disease (PD) is often accompanied by other types of tremor such as action tremor, which includes postural tremor, kinetic tremor, re-emergent tremor (ReT), and orthostatic tremor (OT). Literature on other tremors of PD, especially ReT and OT, is scarce. Tremor can be present in any of the atypical parkinsonian disorders such as progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. RT can even be the presenting symptom of these disorders...
September 2017: Neurology India
https://www.readbyqxmd.com/read/28874525/differential-diagnosis-of-alzheimer-s-disease-using-spectrochemical-analysis-of-blood
#7
Maria Paraskevaidi, Camilo L M Morais, Kássio M G Lima, Julie S Snowden, Jennifer A Saxon, Anna M T Richardson, Matthew Jones, David M A Mann, David Allsop, Pierre L Martin-Hirsch, Francis L Martin
The progressive aging of the world's population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28843020/clinicopathologic-discrepancies-in-a-population-based-incidence-study-of-parkinsonism-in-olmsted-county-1991-2010
#8
Pierpaolo Turcano, Michelle M Mielke, Keith A Josephs, James H Bower, Joseph E Parisi, Bradley F Boeve, Rodolfo Savica
OBJECTIVE: The purpose of this study was to examine the discrepancies between the clinical diagnosis of parkinsonism and neuropathological findings in a population-based cohort with parkinsonian disorders. BACKGROUND: The specific clinical diagnosis of parkinsonism is challenging, and definite confirmation requires neuropathological evaluation. Currently, autopsies are seldom performed, and most brain autopsies represent atypical or diagnostically unresolved cases...
August 26, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28840137/uptake-index-of-123-i-metaiodobenzylguanidine-myocardial-scintigraphy-for-diagnosing-lewy-body-disease
#9
Yoshito Kamiya, Satoru Ota, Shintaro Okumiya, Kosuke Yamashita, Akihiro Takaki, Shigeki Ito
OBJECTIVES: Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy has been used to evaluate cardiac sympathetic denervation in Lewy body disease (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The heart-to-mediastinum ratio (H/M) in PD and DLB is significantly lower than that in Parkinson's plus syndromes and Alzheimer's disease. Although this ratio is useful for distinguishing LBD from non-LBD, it fluctuates depending on the system performance of the gamma cameras...
2017: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/28835999/glucocerebrosidase-expression-patterns-in-the-non-human-primate-brain
#10
Iria G Dopeso-Reyes, Diego Sucunza, Alberto J Rico, Diego Pignataro, David Marín-Ramos, Elvira Roda, Ana I Rodríguez-Pérez, José L Labandeira-García, José L Lanciego
Glucocerebrosidase (GCase) is a lysosomal enzyme encoded by the GBA1 gene. Mutations in GBA1 gene lead to Gaucher's disease, the most prevalent lysosomal storage disorder. GBA1 mutations reduce GCase activity, therefore promoting the aggregation of alpha-synuclein, a common neuropathological finding underlying Parkinson's disease (PD) and dementia with Lewy bodies. However, it is also worth noting that a direct link between GBA1 mutations and alpha-synuclein aggregation indicating cause and effect is still lacking, with limited experimental evidence to date...
August 23, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28833467/dopamine-transporter-imaging-deficit-predicts-early-transition-to-synucleinopathy-in-idiopathic-rem-sleep-behavior-disorder
#11
Alex Iranzo, Joan Santamaría, Francesc Valldeoriola, Monica Serradell, Manel Salamero, Carles Gaig, Aida Niñerola-Baizan, Raquel Sánchez-Valle, Albert Lladó, Roberto De Marzi, Ambra Stefani, Klaus Seppi, Javier Pavia, Birgit Högl, Werner Poewe, Eduard Tolosa, Francesc Lomeña
OBJECTIVE: To determine the usefulness of dopamine transporter (DAT) imaging to identify idiopathic REM sleep behavior disorder (IRBD) patients at risk for short-term development of clinically-defined synucleinopathy. METHODS: Eighty-seven patients with polysomnography-confirmed IRBD underwent (123) I-FP-CIT DAT-SPECT. Results were compared with 20 matched controls without RBD who underwent DAT-SPECT. In patients, FP-CIT uptake was considered abnormal when values were two standard deviations below controls' mean uptake...
August 22, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28829427/recombinant-%C3%AE-%C3%AE-and-%C3%AE-synucleins-stimulate-protein-phosphatase-2a-catalytic-subunit-activity-in-cell-free-assays
#12
Sovanarak Lek, Javier Vargas-Medrano, Ernesto Villanueva, Brian Marcus, Wesley Godfrey, Ruth G Perez
α-Synuclein (aSyn), β-Synuclein (bSyn), and γ-Synuclein (gSyn) are members of a conserved family of chaperone-like proteins that are highly expressed in vertebrate neuronal tissues. Of the three synucleins, only aSyn has been strongly implicated in neurodegenerative disorders such as Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy. In studying normal aSyn function, data indicate that aSyn stimulates the activity of the catalytic subunit of an abundantly expressed dephosphorylating enzyme, PP2Ac in vitro and in vivo...
August 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28828740/the-oligomer-hypothesis-in-%C3%AE-synucleinopathy
#13
REVIEW
Kenjiro Ono
Lewy bodies and Lewy neurites in the brain constitute the main histopathological features of Parkinson's disease (PD) and dementia with Lewy bodies. They comprise amyloid-like fibrils composed of α-synuclein (αS), a small protein (~14 kDa). Because the aggregation of αS in the brain has been implicated as a critical step in the development of these diseases, the research for disease-modifying drugs has focused on modification of the αS aggregation process in the brain. Recent studies using synthetic αS peptides, a cell culture model, transgenic mice models, and human samples such as cerebrospinal fluids and the blood of PD patients have suggested that pre-fibrillar forms of αS (i...
August 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28808912/molecular-imaging-and-updated-diagnostic-criteria-in-lewy-body-dementias
#14
REVIEW
Nicolaas I Bohnen, Martijn L T M Müller, Kirk A Frey
PURPOSE OF REVIEW: The aims of the study were to review recent advances in molecular imaging in the Lewy body dementias (LBD) and determine if these may support the clinical but contested temporal profile distinction between Parkinson disease (PD) with dementia (PDD) versus dementia with Lewy bodies (DLB). RECENT FINDINGS: There do not appear to be major regional cerebral metabolic or neurotransmitter distinctions between PDD and DLB. However, recent studies highlight the relative discriminating roles of Alzheimer proteinopathies...
August 14, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28800743/an-itraq-based-proteomic-analysis-reveals-dysregulation-of-neocortical-synaptopodin-in-lewy-body-dementias
#15
Arnab Datta, Yuek Ling Chai, Jing Min Tan, Jasinda H Lee, Paul T Francis, Christopher P Chen, Siu Kwan Sze, Mitchell K P Lai
Lewy body dementias are the second most common cause of neurodegenerative dementia in the elderly after Alzheimer's disease (AD). The two clinical subgroups of Lewy body dementias, namely, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), are differentiated by the chronology of cognitive symptoms relative to parkinsonism. At present, there remains a debate on whether DLB and PDD are separate disease entities, or fall within the same spectrum of Lewy body dementias. In this study, we compared the detergent-soluble proteome via an 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) analysis of pooled lysates from the prefrontal cortex (BA9) of DLB (n = 19) and PDD (n = 21) patients matched a priori for amyloid (total Aβ42) burden, semi-quantitative scores for Lewy bodies and neurofibrillary tangles together with age-matched control (n = 21) subjects...
August 11, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28798667/the-foxp2-driven-network-in-developmental-disorders-and-neurodegeneration
#16
Franz Oswald, Patricia Klöble, André Ruland, David Rosenkranz, Bastian Hinz, Falk Butter, Sanja Ramljak, Ulrich Zechner, Holger Herlyn
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28756177/dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-become-the-same-disease
#17
Joseph H Friedman
INTRODUCTION: The question whether DLB and PDD are distinct disorders has been debated in several forums. The two disorders, once parkinsonism is present in DLB, cannot be distinguished on clinical or pathological grounds. The conundrum exists for those DLB patients who do not yet have parkinsonism, and raises the parallel with patients who have Rapid Eye Movement Behavior Disorder but have not yet manifested parkinsonian signs. METHODS: A literature review was summarized to justify classification as a single disorder...
July 18, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28751258/distinct-%C3%AE-synuclein-strains-and-implications-for-heterogeneity-among-%C3%AE-synucleinopathies
#18
REVIEW
Chao Peng, Ronald J Gathagan, Virginia M-Y Lee
The deposition of misfolded β-sheet enriched amyloid protein is a shared feature of many neurodegenerative diseases. Recent studies demonstrated the existence of conformationally diverse strains as a common property for multiple amyloidogenic proteins including α-Synuclein (α-Syn). α-Syn is misfolded and aggregated in a group of neurodegenerative diseases collectively known as α-Synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy body, multiple system atrophy and also a subset of Alzheimer's disease patients with concomitant PD-like Lewy bodies and neurites...
July 24, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28750675/differential-role-of-csf-fatty-acid-binding-protein-3-%C3%AE-synuclein-and-alzheimer-s-disease-core-biomarkers-in-lewy-body-disorders-and-alzheimer-s-dementia
#19
Davide Chiasserini, Leonardo Biscetti, Paolo Eusebi, Nicola Salvadori, Giulia Frattini, Simone Simoni, Naomi De Roeck, Nicola Tambasco, Erik Stoops, Hugo Vanderstichele, Sebastiaan Engelborghs, Brit Mollenhauer, Paolo Calabresi, Lucilla Parnetti
BACKGROUND: Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB) share clinical and molecular features. Cerebrospinal fluid (CSF) biomarkers may help the characterization of these diseases, improving the differential diagnosis. We evaluated the diagnostic performance of five CSF biomarkers across a well-characterized cohort of patients diagnosed with AD, DLB, PDD, and Parkinson's disease (PD). METHODS: A total of 208 patients were enrolled in 3 European centers...
July 28, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28734699/an-update-on-the-genetics-of-dementia-with-lewy-bodies
#20
REVIEW
Leonie J M Vergouw, Inger van Steenoven, Wilma D J van de Berg, Charlotte E Teunissen, John C van Swieten, Vincenzo Bonifati, Afina W Lemstra, Frank Jan de Jong
The genetic architecture of dementia with Lewy bodies (DLB) is increasingly taking shape. Initially, genetic research focused mainly on linkage and candidate gene studies in small series of DLB patients. More recently, association and exome sequencing studies in larger groups have been conducted, and have shown that several variants in GBA and the APOE ε4 allele are important genetic risk factors for DLB. However, genetic research in DLB is still in its infancy. So far, many genetic studies have been biased and performed in clinically and pathologically heterogeneous populations...
July 13, 2017: Parkinsonism & related Disorders
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