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https://www.readbyqxmd.com/read/28645308/neonatal-aav-delivery-of-alpha-synuclein-induces-pathology-in-the-adult-mouse-brain
#1
Marion Delenclos, Ayman H Faroqi, Mei Yue, Aishe Kurti, Monica Castanedes-Casey, Linda Rousseau, Virginia Phillips, Dennis W Dickson, John D Fryer, Pamela J McLean
Abnormal accumulation of alpha-synuclein (αsyn) is a pathological hallmark of Lewy body related disorders such as Parkinson's disease and Dementia with Lewy body disease. During the past two decades, a myriad of animal models have been developed to mimic pathological features of synucleinopathies by over-expressing human αsyn. Although different strategies have been used, most models have little or no reliable and predictive phenotype. Novel animal models are a valuable tool for understanding neuronal pathology and to facilitate development of new therapeutics for these diseases...
June 23, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28642257/interaction-between-the-fto-gene-body-mass-index-and-depression-meta-analysis-of-13701-individuals
#2
REVIEW
Margarita Rivera, Adam E Locke, Tanguy Corre, Darina Czamara, Christiane Wolf, Ana Ching-Lopez, Yuri Milaneschi, Stefan Kloiber, Sara Cohen-Woods, James Rucker, Katherine J Aitchison, Sven Bergmann, Dorret I Boomsma, Nick Craddock, Michael Gill, Florian Holsboer, Jouke-Jan Hottenga, Ania Korszun, Zoltan Kutalik, Susanne Lucae, Wolfgang Maier, Ole Mors, Bertram Müller-Myhsok, Michael J Owen, Brenda W J H Penninx, Martin Preisig, John Rice, Marcella Rietschel, Federica Tozzi, Rudolf Uher, Peter Vollenweider, Gerard Waeber, Gonneke Willemsen, Ian W Craig, Anne E Farmer, Cathryn M Lewis, Gerome Breen, Peter McGuffin
BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts...
June 22, 2017: British Journal of Psychiatry: the Journal of Mental Science
https://www.readbyqxmd.com/read/28639878/exploring-the-phenotype-in-mild-cognitive-impairment-to-aid-the-prediction-of-those-at-risk-of-transitioning-to-parkinson-disease-and-dementia-with-lewy-bodies
#3
Jennifer Y Y Szeto, Glenda M Halliday, Sharon L Naismith, Simon J G Lewis
To date, only limited research has concurrently investigated the presence of rapid eye movement sleep behavior disorder (RBD) and other features associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB) in people presenting with mild cognitive impairment (MCI). As a first step towards a longitudinal research project, the present study explored the relationships between MCI, RBD, and depression in 108 older adults who presented with subjective memory complaints but were not known to have a neurodegenerative condition...
July 2017: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/28637800/pharmacokinetics-biodistribution-and-radiation-dosimetry-for-89-zr-trastuzumab-in-patients-with-esophagogastric-cancer
#4
Joseph A O'Donoghue, Jason S Lewis, Neeta Pandit-Taskar, Stephen E Fleming, Heiko Schoder, Steven M Larson, Volkan Beylergil, Shutian Ruan, Serge Lyashchenko, Pat B Zanzonico, Wolfgang Andreas Weber, Jorge A Carrasquillo, Yelena Y Janjigian
Trastuzumab with chemotherapy improves clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive esophagogastric adenocarcinoma (EGA). Despite the therapeutic benefit, responses are rarely complete and the majority of patients develop progression. This is the first report evaluating (89)Zr-trastuzumab in HER2-positive EGA in which we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry. Methods: Trastuzumab was conjugated with deferoxamine and radiolabeled with (89)Zr...
June 21, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28637708/hypohydration-impairs-endurance-performance-a-blinded-study
#5
Lewis J James, Jodie Moss, Joshua Henry, Charikleia Papadopoulou, Stephen A Mears
The general scientific consensus is that starting exercise with hypohydration >2% body mass impairs endurance performance/capacity, but most previous studies might be confounded by a lack of subject blinding. This study examined the effect of hypohydration in a single blind manner using combined oral and intragastric rehydration to manipulate hydration status. After familiarization, seven active males (mean ± SD: age 25 ± 2 years, height 1.79 ± 0.07, body mass 78.6 ± 6.2, VO2peak 48 ± 7 mL·kg·min(-1)) completed two randomized trials at 34°C...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28637099/aggregation-and-phosphorylation-of-%C3%AE-synuclein-with-proteinase-k-resistance-in-focal-%C3%AE-synucleinopathy-predominantly-localized-to-the-cardiac-sympathetic-nervous-system
#6
Nei Fukasawa, Takahiro Fukuda, Masato Nagaoka, Tohru Harada, Hiroyuki Takahashi, Masahiro Ikegami
Aggregates of α-synuclein, a major component of Lewy bodies (LBs) and Lewy neurites (LNs), are distributed throughout the nervous system, including the central nervous system (CNS), sympathetic ganglia, enteric nervous system (ENS), cardiac and pelvic plexuses, submandibular gland, adrenal medulla and skin, in incidental Lewy body disease (ILBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure (PAF) [1-3]. Here we report focal α-synucleinopathy predominantly localized to the cardiac sympathetic nervous system (SNS)...
June 21, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28636829/analysis-of-minimally-invasive-esophagectomy-at-a-single-veterans-affairs-medical-center
#7
Matthew D Skancke, Robert A Grossman, Gustavo Marino, Fredrick J Brody, Gregory D Trachiotis
BACKGROUND: To date, there are no published studies focusing on the benefits of minimally invasive esophagectomy (MIE) versus open esophagectomy at a Veterans Affairs Medical Center (VAMC). Our primary outcome was the incidence of esophageal malignancy in the veteran population and the postoperative morbidity following traditional and MIE for malignancy. DESIGN: Retrospective analysis of the incidence of esophageal malignancy at a Veteran Integrated Service Network (VISN) 5 VAMC reported to the VAMC Esophageal Tumor Registry between 2003 and 2016 and outcomes of the veterans who received esophagectomy for malignancy...
June 21, 2017: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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