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Lewy body disease

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https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#1
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633628/olfactory-testing-in-consecutive-patients-referred-with-suspected-dementia
#2
Ib Thrane Christensen, Elna-Marie Larsson, Ida E Holm, Ole B F Nielsen, Stig Andersen
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and early and accurate diagnosis is important. Olfactory dysfunction is an early sign of AD. The contribution by test of olfactory function has been surveyed in AD vs a line of conditions but remains to be settled in the workup of unselected patients referred with suspected dementia. METHODS: We performed a two-step investigation: first, a comparative study of healthy controls and probable AD patients to test the applicability of the chosen scents (cuisine study); second, a study of consecutive patients referred to our geriatric outpatient clinic for suspected dementia with the investigating personnel blinded to the results of the Olfactory Test (blinded study)...
June 20, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28632413/%C3%AE-synuclein-aggregation-modulation-an-emerging-approach-for-the-treatment-of-parkinson-s-disease
#3
Sushil K Singh, Aloke Dutta, Gyan Modi
Parkinson's disease (PD) is a multifactorial progressive neurological disorder. Pathological hallmarks of PD are characterized by the presence of α-synuclein (αSyn) aggregates known as Lewy bodies. αSyn aggregation is one of the leading causes for the neuronal dysfunction and death in PD. It is also associated with neurotransmitter and calcium release. Current therapies of PD are limited to only symptomatic relief without addressing the underlying pathogenic factors of the disease process such as aggregation of αSyn...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28630086/psychosocial-therapy-for-parkinson-s-related-dementia-study-protocol-for-the-invest-randomised-controlled-trial
#4
Sheree A McCormick, Kathryn R McDonald, Sabina Vatter, Vasiliki Orgeta, Ellen Poliakoff, Sarah Smith, Monty A Silverdale, Bo Fu, Iracema Leroi
INTRODUCTION: Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and 'non-motor' symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation...
June 19, 2017: BMJ Open
https://www.readbyqxmd.com/read/28629580/folding-underlies-bidirectional-role-of-gpr37-pael-r-in-parkinson-disease
#5
REVIEW
Lina Leinartaité, Per Svenningsson
Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent role, particularly in relation to Parkinson disease (PD). GPR37 is a substrate for parkin and accumulates abnormally in autosomal recessive juvenile parkinsonism, contributing to endoplasmic reticulum stress and death of dopaminergic neurons...
June 16, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28626918/marinesco-bodies-and-substantia-nigra-neuron-density-in-parkinson-s-disease
#6
Robert D Abbott, James S Nelson, G Webster Ross, Jane H Uyehara-Lock, Caroline M Tanner, Kamal H Masaki, Lenore J Launer, Lon R White, Helen Petrovitch
AIM: Marinesco bodies (MB) are intranuclear inclusions in pigmented neurons of the substantia nigra (SN). While rare in children, frequency increases with normal aging and is high in Alzheimer's disease, dementia with Lewy bodies, and other neurodegenerative disorders. Coinciding with the age-related rise in MB frequency is initiation of cell death among SN neurons. Whether MB have a role in this process is unknown. Our aim is to examine the association of MB with SN neuron density in Parkinson's disease (PD) in the Honolulu-Asia Aging Study...
June 19, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28625940/prodromal-stage-of-disease-dementia-with-lewy-bodies-how-to-diagnose-in-practice
#7
Frédéric Blanc, Marc Verny
Disease with Lewy bodies or dementia with Lewy bodies (DLB), particularly at the prodromal stage, is a complex disease to diagnose because of different clinical beginnings and variable paths in terms of clinical expression. Thus DLB can be entcountered in different input modes: mild cognitive impairment, depression, acute behavioral disorders, confusion and delirium, or sleep disorders. In the aim to better diagnose the disease, should be sought obviously to search for the key symptoms: fluctuations, hallucinations, extra-pyramidal syndrome, and REM sleep behavior disorder...
June 1, 2017: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
https://www.readbyqxmd.com/read/28622212/a-retrospective-study-of-pimavanserin-use-in-a-movement-disorders-clinic
#8
Joseph H Friedman
Pimavanserin, a 5-HT2A inverse agonist, was commercially released in the United States in April 2016 for the treatment of Parkinson disease psychosis. No "naturalistic" treatment results have yet been published. Charts from the movement disorders clinic were reviewed for all patients who received this drug as treatment for psychosis associated with primary parkinsonism due to α-synucleinopathies. Data of 10 patients with idiopathic Parkinson disease, including 1 with a long history of schizophrenia, 4 with dementia with Lewy bodies, and 1 with multiple-system atrophy, were reviewed...
June 16, 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28619113/mechanisms-underlying-extensive-ser129-phosphorylation-in-%C3%AE-synuclein-aggregates
#9
Shigeki Arawaka, Hiroyasu Sato, Asuka Sasaki, Shingo Koyama, Takeo Kato
Parkinson's disease (PD) is characterized neuropathologically by intracellular aggregates of fibrillar α-synuclein, termed Lewy bodies (LBs). Approximately 90% of α-synuclein deposited as LBs is phosphorylated at Ser129 in brains with PD. In contrast, only 4% of total α-synuclein is phosphorylated at Ser129 in brains with normal individuals. It is unclear why extensive phosphorylation occurs in the pathological process of PD. To address this issue, we investigated a mechanism and role of Ser129-phosphorylation in regulating accumulation of α-synuclein...
June 15, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28617831/depression-in-dementia-with-lewy-bodies-a-comparison-with-alzheimer-s-disease
#10
Pai-Yi Chiu, Chein-Wei Wang, Chun-Tang Tsai, Shin-Hua Li, Chih-Li Lin, Te-Jen Lai
BACKGROUND: Depression is highly associated with dementia, and this study will compare the frequencies, severity, and symptoms of depression between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: Frequency of depression was determined according to the DSM-IV criteria for major depression or the National Institute of Mental Health criteria for depression in AD (NIMH-dAD). Severity of depression were assessed using the Hamilton Depression Rating Scale, the Cornell Scale for Depression in Dementia, and the depression subscale in Neuropsychiatric Inventory...
2017: PloS One
https://www.readbyqxmd.com/read/28614796/%C3%AE-synuclein-in-gut-endocrine-cells-and-its-implications-for-parkinson-s-disease
#11
Rashmi Chandra, Annie Hiniker, Yien-Ming Kuo, Robert L Nussbaum, Rodger A Liddle
Parkinson's disease (PD) is a progressive neurodegenerative disease with devastating clinical manifestations. In PD, neuronal death is associated with intracellular aggregates of the neuronal protein α-synuclein known as Lewy bodies. Although the cause of sporadic PD is not well understood, abundant clinical and pathological evidence show that misfolded α-synuclein is found in enteric nerves before it appears in the brain. This suggests a model in which PD pathology originates in the gut and spreads to the central nervous system via cell-to-cell prion-like propagation, such that transfer of misfolded α-synuclein initiates misfolding of native α-synuclein in recipient cells...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28613396/evaluation-of-acetylcholinesterase-and-carbonic-anhydrase-inhibition-profiles-of-1-2-3-4-6-pentasubstituted-4-hydroxy-cyclohexanes
#12
Umit M Kocyigit, Parham Taslimi, Hayreddin Gezegen, İlhami Gulçin, Mustafa Ceylan
Carbonic anhydrase (CA; EC 4.2.1.1) is used for remedial purposes for several years, as there is significant focus on expanding more new activators (CAAs) and high affinity inhibitors. Alzheimer's disease and other similar ailments such as dementia and vascular dementia with Lewy bodies reduce cholinergic activity in the important areas involved in cognition and memory. Prevalent drugs for the symptomatic therapy of dementia are significant in increasing the associated cholinergic deficiency by inhibiting acetylcholinesterase (AChE)...
June 14, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28609445/estimating-the-causal-influence-of-body-mass-index-on-risk-of-parkinson-disease-a-mendelian-randomisation-study
#13
Alastair J Noyce, Demis A Kia, Gibran Hemani, Aude Nicolas, T Ryan Price, Eduardo De Pablo-Fernandez, Philip C Haycock, Patrick A Lewis, Thomas Foltynie, George Davey Smith, Anette Schrag, Andrew J Lees, John Hardy, Andrew Singleton, Mike A Nalls, Neil Pearce, Debbie A Lawlor, Nicholas W Wood
BACKGROUND: Both positive and negative associations between higher body mass index (BMI) and Parkinson disease (PD) have been reported in observational studies, but it has been difficult to establish causality because of the possibility of residual confounding or reverse causation. To our knowledge, Mendelian randomisation (MR)-the use of genetic instrumental variables (IVs) to explore causal effects-has not previously been used to test the effect of BMI on PD. METHODS AND FINDINGS: Two-sample MR was undertaken using genome-wide association (GWA) study data...
June 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28603772/compensatory-shifts-in-visual-perception-are-associated-with-hallucinations-in-lewy-body-disorders
#14
Alan Robert Bowman, Vicki Bruce, Christopher J Colbourn, Daniel Collerton
Visual hallucinations are a common, distressing, and disabling symptom of Lewy body and other diseases. Current models suggest that interactions in internal cognitive processes generate hallucinations. However, these neglect external factors. Pareidolic illusions are an experimental analogue of hallucinations. They are easily induced in Lewy body disease, have similar content to spontaneous hallucinations, and respond to cholinesterase inhibitors in the same way. We used a primed pareidolia task with hallucinating participants with Lewy body disorders (n = 16), non-hallucinating participants with Lewy body disorders (n = 19), and healthy controls (n = 20)...
2017: Cognitive Research: Principles and Implications
https://www.readbyqxmd.com/read/28602509/neurochip-an-updated-version-of-the-neurox-genotyping-platform-to-rapidly-screen-for-variants-associated-with-neurological-diseases
#15
Cornelis Blauwendraat, Faraz Faghri, Lasse Pihlstrom, Joshua T Geiger, Alexis Elbaz, Suzanne Lesage, Jean-Christophe Corvol, Patrick May, Aude Nicolas, Yevgeniya Abramzon, Natalie A Murphy, J Raphael Gibbs, Mina Ryten, Raffaele Ferrari, Jose Bras, Rita Guerreiro, Julie Williams, Rebecca Sims, Steven Lubbe, Dena G Hernandez, Kin Y Mok, Laurie Robak, Roy H Campbell, Ekaterina Rogaeva, Bryan J Traynor, Ruth Chia, Sun Ju Chung, John A Hardy, Alexis Brice, Nicholas W Wood, Henry Houlden, Joshua M Shulman, Huw R Morris, Thomas Gasser, Rejko Krüger, Peter Heutink, Manu Sharma, Javier Simón-Sánchez, Mike A Nalls, Andrew B Singleton, Sonja W Scholz
Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurodegenerative diseases. Here, we present its updated version, named NeuroChip. The NeuroChip is a low-cost, custom-designed array containing a tagging variant backbone of about 306,670 variants complemented with a manually curated custom content comprised of 179,467 variants implicated in diverse neurological diseases, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy...
May 17, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28600444/deconstructing-psychosis-and-misperception-symptoms-in-parkinson-s-disease
#16
Yoshiyuki Nishio, Kayoko Yokoi, Makoto Uchiyama, Yasuyuki Mamiya, Hiroyuki Watanabe, Miyeong Gang, Toru Baba, Atsushi Takeda, Kazumi Hirayama, Etsuro Mori
OBJECTIVE: Patients with Lewy body disease develop a variety of psychotic and misperception symptoms, including visual hallucinations and delusions, as well as 'minor hallucinations', that is, a sense of presence, passage hallucinations and visual illusions. Although these symptoms have been suggested to have common underlying mechanisms, the commonalities and differences among them have not been systematically investigated at the neural level. METHODS: Sixty-seven patients with Parkinson's disease underwent neuropsychological and behavioural assessments, volumetric MRI and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)...
June 9, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28599681/brain-derived-exosomes-from-dementia-with-lewy-bodies-propagate-%C3%AE-synuclein-pathology
#17
Jennifer Ngolab, Ivy Trinh, Edward Rockenstein, Michael Mante, Jazmin Florio, Margarita Trejo, Deborah Masliah, Anthony Adame, Eliezer Masliah, Robert A Rissman
Proteins implicated in neurodegenerative conditions such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have been identified in bodily fluids encased in extracellular vesicles called exosomes. Whether exosomes found in DLB patients can transmit pathology is not clear. In this study, exosomes were successfully harvested through ultracentrifugation from brain tissue from DLB and AD patients as well as non-diseased brain tissue. Exosomes extracted from brains diagnosed with either AD or DLB contained aggregate-prone proteins...
June 9, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28595550/new-tracers-and-new-perspectives-for-molecular-imaging-in-lewy-body-diseases
#18
Matteo Bauckneht, Dario Arnaldi, Flavio Nobili, Dag Aarsland, Silvia Morbelli
The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA) and idiopatic Rem Sleeping behaviour disorders (RBD) complete the group of synucleinopathies and have also common symptoms with respect to LBDs. The clinical diagnosis of LBDs can be challenging for physicians, particularly in the early stages of disease...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28592453/diagnosis-and-management-of-dementia-with-lewy-bodies-fourth-consensus-report-of-the-dlb-consortium
#19
REVIEW
Ian G McKeith, Bradley F Boeve, Dennis W Dickson, Glenda Halliday, John-Paul Taylor, Daniel Weintraub, Dag Aarsland, James Galvin, Johannes Attems, Clive G Ballard, Ashley Bayston, Thomas G Beach, Frédéric Blanc, Nicolaas Bohnen, Laura Bonanni, Jose Bras, Patrick Brundin, David Burn, Alice Chen-Plotkin, John E Duda, Omar El-Agnaf, Howard Feldman, Tanis J Ferman, Dominic Ffytche, Hiroshige Fujishiro, Douglas Galasko, Jennifer G Goldman, Stephen N Gomperts, Neill R Graff-Radford, Lawrence S Honig, Alex Iranzo, Kejal Kantarci, Daniel Kaufer, Walter Kukull, Virginia M Y Lee, James B Leverenz, Simon Lewis, Carol Lippa, Angela Lunde, Mario Masellis, Eliezer Masliah, Pamela McLean, Brit Mollenhauer, Thomas J Montine, Emilio Moreno, Etsuro Mori, Melissa Murray, John T O'Brien, Sotoshi Orimo, Ronald B Postuma, Shankar Ramaswamy, Owen A Ross, David P Salmon, Andrew Singleton, Angela Taylor, Alan Thomas, Pietro Tiraboschi, Jon B Toledo, John Q Trojanowski, Debby Tsuang, Zuzana Walker, Masahito Yamada, Kenji Kosaka
The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and (123)iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy...
June 7, 2017: Neurology
https://www.readbyqxmd.com/read/28592304/post-translational-changes-to-%C3%AE-synuclein-control-iron-and-dopamine-trafficking-a-concept-for-neuron-vulnerability-in-parkinson-s-disease
#20
REVIEW
James A Duce, Bruce X Wong, Hannah Durham, Jean-Christophe Devedjian, David P Smith, David Devos
Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking...
June 7, 2017: Molecular Neurodegeneration
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