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https://www.readbyqxmd.com/read/28529891/biomonitorization-of-iron-accumulation-in-the-substantia-nigra-from-lewy-body-disease-patients
#1
Belén Fernández, Isidro Ferrer, Fernando Gil, Sabine Hilfiker
Iron levels in the healthy human brain are known to be high in certain areas such as the substantia nigra (SN), and increase further with age. In addition, there is some evidence for a further increase in iron load in the SN of Parkinson's disease (PD) patients as compared to controls, which correlates with motor disability. Here, we have analyzed total iron levels in cells as well as mouse and human brain samples by atomic absorption spectroscopy (AAS). Our data indicate that iron load is more pronounced in cells with dopaminergic features...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28528348/effect-of-home-noninvasive-ventilation-with-oxygen-therapy-vs-oxygen-therapy-alone-on-hospital-readmission-or-death-after-an-acute-copd-exacerbation-a-randomized-clinical-trial
#2
Patrick B Murphy, Sunita Rehal, Gill Arbane, Stephen Bourke, Peter M A Calverley, Angela M Crook, Lee Dowson, Nicholas Duffy, G John Gibson, Philip D Hughes, John R Hurst, Keir E Lewis, Rahul Mukherjee, Annabel Nickol, Nicholas Oscroft, Maxime Patout, Justin Pepperell, Ian Smith, John R Stradling, Jadwiga A Wedzicha, Michael I Polkey, Mark W Elliott, Nicholas Hart
Importance: Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective: To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants: A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015...
May 21, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28527219/tmem230-accumulation-in-granulovacuolar-degeneration-bodies-and-dystrophic-neurites-of-alzheimer-s-disease
#3
Sandra L Siedlak, Yingfei Jiang, Mikayla L Huntley, Luwen Wang, Ju Gao, Fei Xie, Jingyi Liu, Bo Su, George Perry, Xinglong Wang
Transmembrane Protein 230 (TMEM230) is a newly identified protein associated with Parkinson's disease (PD) found in Lewy bodies and Lewy neurites of patients with PD or dementia with Lewy body disease. However, TMEM230 has not yet been investigated in the most common neurodegenerative disorder, Alzheimer's disease (AD). Here, we demonstrate that the expression of TMEM230 is specifically increased in neurons in AD patients. Importantly, both granulovacuolar degeneration (GVD) and dystrophic neurites (DNs), two prominent characteristic pathological structures associated with AD, contain TMEM230 aggregates...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527044/endocytic-vesicle-rupture-is-a-conserved-mechanism-of-cellular-invasion-by-amyloid-proteins
#4
William P Flavin, Luc Bousset, Zachary C Green, Yaping Chu, Stratos Skarpathiotis, Michael J Chaney, Jeffrey H Kordower, Ronald Melki, Edward M Campbell
Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis...
May 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28522732/unbiased-proteomics-of-early-lewy-body-formation-model-implicates-active-microtubule-affinity-regulating-kinases-marks-in-synucleinopathies
#5
Michael X Henderson, Charlotte Hiu-Yan Chung, Dawn M Riddle, Bin Zhang, Ronald J Gathagan, Steven H Seeholzer, John Q Trojanowski, Virginia M Y Lee
Parkinson's disease (PD) patients progressively accumulate intracytoplasmic inclusions formed by misfolded α-synuclein known as Lewy bodies (LBs). LBs also contain other proteins that may or may not be relevant in the disease process. To identify proteins involved early in LB formation, we performed proteomic analysis of insoluble proteins in a primary neuron culture model of α-synuclein pathology. We identified proteins previously found in authentic LBs in PD as well as several novel proteins, including the microtubule affinity-regulating kinase 1 (MARK1), one of the most enriched proteins in this model of LB formation...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28516990/cross-talk-between-neurometals-and-amyloidogenic-proteins-at-the-synapse-and-the-pathogenesis-of-neurodegenerative-diseases
#6
REVIEW
M Kawahara, M Kato-Negishi, K Tanaka
Increasing evidence suggests that disruption of metal homeostasis contributes to the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease, prion diseases, Lewy body diseases, and vascular dementia. Conformational changes of disease-related proteins (amyloidogenic proteins), such as β-amyloid protein, prion proteins, and α-synuclein, are well-established contributors to neurotoxicity and to the pathogenesis of these diseases. Recent studies have demonstrated that these amyloidogenic proteins are metalloproteins that bind trace elements, including zinc, iron, copper, and manganese, and play significant roles in the maintenance of metal homeostasis...
May 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#7
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28515265/clinical-marker-for-alzheimer-disease-pathology-in-logopenic-primary-progressive-aphasia
#8
Lucia A A Giannini, David J Irwin, Corey T McMillan, Sharon Ash, Katya Rascovsky, David A Wolk, Vivianna M Van Deerlin, Edward B Lee, John Q Trojanowski, Murray Grossman
OBJECTIVE: To determine whether logopenic features of phonologic loop dysfunction reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia (PPA). METHODS: We performed a retrospective case-control study of 34 patients with PPA with available autopsy tissue. We compared baseline and longitudinal clinical features in patients with primary AD neuropathology to those with primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in pathology-defined groups using postmortem neuropathologic data...
May 17, 2017: Neurology
https://www.readbyqxmd.com/read/28513079/rem-sleep-behavior-disorder-in-parkinson-s-disease-and-other-synucleinopathies
#9
REVIEW
Erik K St Louis, Angelica R Boeve, Bradley F Boeve
Rapid eye movement sleep behavior disorder is characterized by dream enactment and complex motor behaviors during rapid eye movement sleep and rapid eye movement sleep atonia loss (rapid eye movement sleep without atonia) during polysomnography. Rapid eye movement sleep behavior disorder may be idiopathic or symptomatic and in both settings is highly associated with synucleinopathy neurodegeneration, especially Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure...
May 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28505261/survival-and-causes-of-death-among-people-with-clinically-diagnosed-synucleinopathies-with-parkinsonism-a-population-based-study
#10
Rodolfo Savica, Brandon R Grossardt, James H Bower, J Eric Ahlskog, Bradley F Boeve, Jonathan Graff-Radford, Walter A Rocca, Michelle M Mielke
Importance: To our knowledge, a comprehensive study of the survival and causes of death of persons with synucleinopathies compared with the general population has not been conducted. Understanding the long-term outcomes of these conditions may inform patients and caregivers of the expected disease duration and may help with care planning. Objective: To compare survival rates and causes of death among patients with incident, clinically diagnosed synucleinopathies and age- and sex-matched referent participants...
May 15, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28504037/plasma-butyrylcholinesterase-activity-a-possible-biomarker-for-differential-diagnosis-between-alzheimer-s-disease-and-dementia-with-lewy-bodies
#11
N D Josviak, M S Batistela, R K M Souza, N R Wegner, G F Bono, C D Sulzbach, D P Simão-Silva, M R Piovezan, R L R Souza, L Furtado-Alle
Butyrylcholinesterase (BChE) is an enzyme encoded by BCHE gene, responsible for catalyzing the hydrolysis of acetylcholine. K and -116A BCHE variants were associated with decrease in plasma BChE activity, and their influence has been investigated in diseases with a cholinergic deficit such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). In order to check the influence of BCHE genetic variants on enzymatic activity, all patients and controls were genotyped for K and -116A variants. We found lower plasma BChE activity in DLB patients compared to elderly controls and to AD independent of the presence of K or -116A variants...
May 15, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28499012/resistance-to-alzheimer-disease-neuropathologic-changes-and-apparent-cognitive-resilience-in-the-nun-and-honolulu-asia-aging-studies
#12
Caitlin S Latimer, C Dirk Keene, Margaret E Flanagan, Laura S Hemmy, Kelvin O Lim, Lon R White, Kathleen S Montine, Thomas J Montine
Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28495859/alpha-synuclein-may-cross-bridge-v-snare-and-acidic-phospholipids-to-facilitate-snare-dependent-vesicle-docking
#13
Xiaochu Lou, Jaewook Kim, Brenden J Hawk, Yeon-Kyun Shin
Misfolded α-synuclein/A-syn is widely recognized as primal cause of neurodegenerative diseases including Parkinson's and dementia with Lewy bodies. The normal cellular function of A-syn has however been elusive. There is evidence that A-syn plays a variety of roles in the exocytotic pathway in the neuron, but the underlying molecular mechanisms are unclear. A-syn has been known to interact with negatively charged phospholipids and with vesicle SNARE protein VAMP2 as well. Using single vesicle-vesicle docking/fusion assays, we find that A-syn promotes SNARE-dependent vesicles docking significantly at 2...
May 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28491896/physical-activity-predicts-reduced-plasma-%C3%AE-amyloid-in-the-cardiovascular-health-study
#14
Chelsea M Stillman, Oscar L Lopez, James T Becker, Lewis H Kuller, Pankaj D Mehta, Russell P Tracy, Kirk I Erickson
OBJECTIVE: Higher levels of physical activity (PA) reduce the risk of cognitive impairment, but the underlying mechanisms are unclear. Using longitudinal data from the Cardiovascular Health Study, we examined whether PA predicted plasma Aβ levels and risk for cognitive decline 9-13 years later. METHODS: Linear and logistic regressions (controlling for APOE status, age, gender, body mass index, cardiovascular disease, brain white matter lesions, and cystatin C levels) tested associations between PA, Aβ, and cognitive impairment in a sample of 149 cognitively normal older adults (mean age 83 years)...
May 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28488154/impact-of-multiple-pathologies-on-the-threshold-for-clinically-overt-dementia
#15
REVIEW
Alifiya Kapasi, Charles DeCarli, Julie A Schneider
Longitudinal clinical-pathological studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and cerebrovascular disease pathologies) as important factors in the development of Alzheimer's disease (AD) and other forms of dementia. Older persons with AD pathology, often have concomitant cerebrovascular disease pathologies (macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy) as well as other concomitant neurodegenerative disease pathologies (Lewy bodies, TDP-43, hippocampal sclerosis)...
May 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28487947/high-expression-levels-of-the-d686n-parkinson-s-disease-mutation-in-vps35-induces-%C3%AE-synuclein-dependent-toxicity-in-yeast
#16
Yi Huang, Xiang Chen, Xiaofei He, Caifeng Guo, Xicui Sun, Fengyin Liang, Simei Long, Xilin Lu, Luyang Feng, Wenyuan Guo, Yixuan Zeng, Zhong Pei
Parkinson's disease (PD) is a common neurodegenerative disorder that affects ~2% of the human population aged >65. α‑synuclein serves a role in the pathogenesis of PD as it is a primary component of Lewy bodies, a pathological feature of PD. Endosomal‑lysosomal dysfunction may be a key factor involved in the pathophysiology of PD, and may cause PD‑associated neurodegeneration via α‑synuclein‑dependent and ‑independent mechanisms. The D620N mutation in the endosomal‑lysosomal gene, vacuolar protein sorting‑associated protein 35 (VPS35), has been linked to PD...
May 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28482862/higher-levels-of-myelin-phospholipids-in-brains-of-neuronal-%C3%AE-synuclein-transgenic-mice-precede-myelin-loss
#17
Jessica Grigoletto, Katharina Pukaß, Ayelet Gamliel, Dana Davidi, Rachel Katz-Brull, Christiane Richter-Landsberg, Ronit Sharon
α-Synuclein is a protein involved in the pathogenesis of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We investigated the role of neuronal α-Syn in myelin composition and abnormalities. The phospholipid content of purified myelin was determined by (31)P NMR in two mouse lines modeling PD, PrP-A53T α-Syn and Thy-1 wt-α-Syn. Significantly higher levels of phospholipids were detected in myelin purified from brains of these α-Syn transgenic mouse models than in control mice...
May 8, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28479587/structure-distribution-and-genetic-profile-of-%C3%AE-synuclein-and-their-potential-clinical-application-in-parkinson-s-disease
#18
Xiaoli Si, Jiali Pu, Baorong Zhang
Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy...
May 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28474150/association-of-arterial-stiffness-with-cognition-in-patients-with-lewy-body-disorder
#19
Dong-Woo Ryu, Joong-Seok Kim, Jee-Eun Lee, Jeong-Wook Park, Yoon-Sang Oh, Jae-Young An, Kwang-Soo Lee
The brachial-ankle pulse wave velocity (baPWV) is a marker for arterial stiffness, which is associated with cardiovascular diseases. Arterial stiffness is associated with cognitive function in the elderly and patients with Alzheimer's disease (AD). We aimed to investigate the association between arterial stiffness and cognitive function in patients with Lewy body disorder (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We consecutively included 123 patients with PD, 10 patients with DLB, and 27 AD controls...
May 5, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28473650/a-descriptive-study-of-lewy-body-dementia-with-functional-imaging-support-in-a-chinese-population-a-preliminary-study
#20
Y F Shea, L W Chu, S C Lee
INTRODUCTION: Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia. There have been limited clinical studies among Chinese patients with Lewy body dementia. This study aimed to review the presenting clinical features and identify risk factors for complications including fall, dysphagia, aspiration pneumonia, pressure sores, and mortality in Chinese patients with Lewy body dementia. We also wished to identify any difference in clinical features of patients with Lewy body dementia with and without an Alzheimer's disease pattern of functional imaging...
May 5, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
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