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Lewy body disease

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https://www.readbyqxmd.com/read/28212433/elevated-gm3-plasma-concentration-in-idiopathic-parkinson-s-disease-a-lipidomic-analysis
#1
Robin B Chan, Adler J Perotte, Bowen Zhou, Christopher Liong, Evan J Shorr, Karen S Marder, Un J Kang, Cheryl H Waters, Oren A Levy, Yimeng Xu, Hong Bin Shim, Itsik Pe'er, Gilbert Di Paolo, Roy N Alcalay
Parkinson's disease (PD) is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomic studies in PD are lacking. In the current study, we analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the 'Spot' study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid subclasses including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols...
2017: PloS One
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#2
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28210978/future-directions-in-imaging-neurodegeneration
#3
REVIEW
Joseph C Masdeu
Neuroimaging comprises a powerful set of instruments to diagnose various neurodegenerative disorders, clarifies their neurobiology, and monitors their treatment. Magnetic resonance imaging depicts volume changes, as well as abnormalities in functional and structural connectivity. Positron emission tomography (PET) allows for the quantification of regional cerebral metabolism, characteristically altered in Alzheimer's disease, amyotrophic lateral sclerosis, diffuse Lewy-body disease, and the frontotemporal dementias...
January 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28205015/self-management-of-dietary-intake-using-mindful-eating-to-improve-dietary-intake-for-individuals-with-early-stage-chronic-kidney-disease
#4
Gayle M Timmerman, Muna J Tahir, Richard M Lewis, Deborah Samoson, Holli Temple, Michele R Forman
Using mindful eating to improve specific dietary recommendations has not been adequately studied. This feasibility study examined an intervention, self-management of dietary intake using mindful eating, with 19 participants that had mild to moderate chronic kidney disease, using a prospective, single group, pretest-posttest design. The intervention had six weekly classes focused on self-management using mindful eating, goal-setting, problem-solving, and food label reading. Weight, body mass index (BMI), 3-day 24-h dietary recalls and fasting blood samples were measured...
February 15, 2017: Journal of Behavioral Medicine
https://www.readbyqxmd.com/read/28205009/mixed-pathologies-including-chronic-traumatic-encephalopathy-account-for-dementia-in-retired-association-football-soccer-players
#5
Helen Ling, Huw R Morris, James W Neal, Andrew J Lees, John Hardy, Janice L Holton, Tamas Revesz, David D R Williams
In retired professional association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career, and concussion history were prospectively collected. Next-of-kin provided consent for six to have post-mortem brain examination. Of the 14 male participants, 13 were professional and 1 was a committed amateur...
February 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28202694/pure-autonomic-failure-predictors-of-conversion-to-clinical-cns-involvement
#6
Wolfgang Singer, Sarah E Berini, Paola Sandroni, Robert D Fealey, Elizabeth A Coon, Mariana D Suarez, Eduardo E Benarroch, Phillip A Low
OBJECTIVE: Based on the observation that a subset of patients originally diagnosed with pure autonomic failure (PAF) eventually develops extrapyramidal or cerebellar involvement consistent with multiple system atrophy (MSA), Parkinson disease (PD), or dementia with Lewy bodies (DLB), we aimed to identify predictors of progression of PAF to more sinister synucleinopathies. METHODS: In this retrospective cohort study, we reviewed patients seen at Mayo Clinic Rochester by autonomic specialists between 2001 and 2011 and during initial evaluation diagnosed with orthostatic hypotension consistent with PAF (possible PAF)...
February 15, 2017: Neurology
https://www.readbyqxmd.com/read/28193887/tmem175-deficiency-impairs-lysosomal-and-mitochondrial-function-and-increases-%C3%AE-synuclein-aggregation
#7
Sarah Jinn, Robert E Drolet, Paige E Cramer, Andus Hon-Kit Wong, Dawn M Toolan, Cheryl A Gretzula, Bhavya Voleti, Galya Vassileva, Jyoti Disa, Marija Tadin-Strapps, David J Stone
Parkinson disease (PD) is a neurodegenerative disorder pathologically characterized by nigrostriatal dopamine neuron loss and the postmortem presence of Lewy bodies, depositions of insoluble α-synuclein, and other proteins that likely contribute to cellular toxicity and death during the disease. Genetic and biochemical studies have implicated impaired lysosomal and mitochondrial function in the pathogenesis of PD. Transmembrane protein 175 (TMEM175), the lysosomal K(+) channel, is centered under a major genome-wide association studies peak for PD, making it a potential candidate risk factor for the disease...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28190674/neuronal-loss-and-%C3%AE-synuclein-pathology-in-the-superior-colliculus-and-its-relationship-to-visual-hallucinations-in-dementia-with-lewy-bodies
#8
Daniel Erskine, Alan J Thomas, John-Paul Taylor, Michael A Savage, Johannes Attems, Ian G McKeith, Christopher M Morris, Ahmad A Khundakar
OBJECTIVE: Patients with dementia with Lewy bodies (DLB) often experience visual hallucinations, which are related to decreased quality of life for patients and increased caregiver distress. The pathologic changes that contribute to visual hallucinations are not known, but several hypotheses implicate deficient attentional processing. The superior colliculus has a role in visual attention and planning eye movements and has been directly implicated in several models of visual hallucinations...
January 10, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28188385/pure-autonomic-failure-without-synucleinopathy
#9
Risa Isonaka, Courtney Holmes, Glen A Cook, Patti Sullivan, Yehonatan Sharabi, David S Goldstein
Pure autonomic failure is a rare form of chronic autonomic failure manifesting with neurogenic orthostatic hypotension and evidence of sympathetic noradrenergic denervation unaccompanied by signs of central neurodegeneration. It has been proposed that pure autonomic failure is a Lewy body disease characterized by intra-neuronal deposition of the protein alpha-synuclein in Lewy bodies and neurites. A middle-aged man with previously diagnosed pure autonomic failure experienced a sudden, fatal cardiac arrest. He was autopsied, and tissues were harvested for neurochemical and immunofluorescence studies...
February 10, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#10
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28181068/laminar-degeneration-of-frontal-and-temporal-cortex-in-parkinson-disease-dementia
#11
Richard A Armstrong
To investigate cortical laminar degeneration in Parkinson's disease (PD) with dementia (PDD). Changes in density of α-synuclein-immunoreactive Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG) together with surviving neurons, abnormally enlarged neurons (EN), vacuoles, and glial cell nuclei were measured across cortical laminae of frontal and temporal cortex in fifteen cases of PDD using quantitative methods and polynomial curve-fitting. Most frequently, LB and LN were distributed across all laminae, while LG were distributed in upper cortical laminae...
February 8, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28177178/association-of-premorbid-personality-with-behavioral-and-psychological-symptoms-in-dementia-with-lewy-bodies-comparison-with-alzheimer-s-disease-patients
#12
Kazuki Tabata, Yasuaki Saijo, Fumiyoshi Morikawa, Juichiro Naoe, Eiji Yoshioka, Yasuyuki Kawanishi, Yoshihiko Nakagi, Takahiko Yoshida
AIM: The aim of this study was to elucidate the relationship between premorbid personality traits and behavioral and psychological symptoms in dementia (BPSD) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients. METHODS: Forty-one DLB patients and 98 AD patients were assessed for BPSD using the Neuropsychiatric Inventory (NPI). Each patient's midlife personality traits were rated by a family member using the NEO Five-Factor Inventory (NEO-FFI) questionnaire...
February 8, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28171705/endothelin-converting-enzymes-degrade-%C3%AE-synuclein-and-are-reduced-in-dementia-with-lewy-bodies
#13
J Scott Miners, Seth Love
We have examined the roles of the endothelin-converting enzyme-1 and -2 (ECE-1 and ECE-2) in the homeostasis of α-synuclein (α-syn) and pathogenesis of Lewy body disease. The ECEs are named for their ability to convert inactive big endothelin to the vasoactive peptide endothelin-1 (EDN1). We have found that ECE-1 and ECE-2 cleave and degrade α-syn in vitro and siRNA-mediated knockdown of ECE-1 and ECE-2 in SH-SY5Y neuroblastoma cells significantly increased α-syn both intracellularly (within the cell lysate) (P < 0...
February 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28170377/%C3%AE-synuclein-toxicity-in-neurodegeneration-mechanism-and-therapeutic-strategies
#14
REVIEW
Yvette C Wong, Dimitri Krainc
Alterations in α-synuclein dosage lead to familial Parkinson's disease (PD), and its accumulation results in synucleinopathies that include PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Furthermore, α-synuclein contributes to the fibrilization of amyloid-b and tau, two key proteins in Alzheimer's disease, which suggests a central role for α-synuclein toxicity in neurodegeneration. Recent studies of factors contributing to α-synuclein toxicity and its disruption of downstream cellular pathways have expanded our understanding of disease pathogenesis in synucleinopathies...
February 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28167817/spotlight-proteomics-uncovering-the-hidden-blood-proteome-improves-diagnostic-power-of-proteomics
#15
Susanna L Lundström, Bo Zhang, Dorothea Rutishauser, Dag Aarsland, Roman A Zubarev
The human blood proteome is frequently assessed by protein abundance profiling using a combination of liquid chromatography and tandem mass spectrometry (LC-MS/MS). In traditional sequence database search, many good-quality MS/MS data remain unassigned. Here we uncover the hidden part of the blood proteome via novel SpotLight approach. This method combines de novo MS/MS sequencing of enriched antibodies and co-extracted proteins with subsequent label-free quantification of new and known peptides in both enriched and unfractionated samples...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167231/nicotine-slows-down-oligomerisation-of-%C3%AE-synuclein-and-ameliorates-cytotoxicity-in-a-yeast-model-of-parkinson-s-disease
#16
Jay Kardani, Ratnika Sethi, Ipsita Roy
Several retrospective epidemiological reports have indicated an inverse correlation between smoking and development of Parkinson's disease (PD). This has mostly been attributed to the neuroprotective role of nicotine in stimulating nicotinic acetylcholine receptors and dopaminergic neurons which are damaged in PD. One of the characteristic features of PD is the intraneuronal deposition of globular inclusions of the intrinsically disordered protein α-synuclein as Lewy bodies. Using in vitro and the well-validated yeast cell models, we show that nicotine also exerts a beneficial effect on aggregation of α-synuclein...
February 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28166276/homovanillic-acid-and-5-hydroxyindole-acetic-acid-as-biomarkers-for-dementia-with-lewy-bodies-and-coincident-alzheimer-s-disease-an-autopsy-confirmed-study
#17
Satoru Morimoto, Masaki Takao, Hiroyuki Hatsuta, Yasushi Nishina, Tadashi Komiya, Renpei Sengoku, Yuta Nakano, Akiko Uchino, Hiroyuki Sumikura, Yuko Saito, Kazutomi Kanemaru, Shigeo Murayama
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aβ) 1-42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia...
2017: PloS One
https://www.readbyqxmd.com/read/28164279/calcipotriol-inhibits-%C3%AE-synuclein-aggregation-in-sh-sy5y-neuroblastoma-cells-by-a-calbindin-d28k-dependent-mechanism
#18
Alexandre N Rcom-H'cheo-Gauthier, Adrian C B Meedeniya, Dean L Pountney
Many neurodegenerative diseases are characterized by the formation of microscopically visible intracellular protein aggregates. α-Synuclein is the key aggregating protein in Parkinson's disease which is characterized by neuronal cytoplasmic Lewy body inclusions. Previous studies have shown relative sparing of neurons in Parkinson's disease and dementia with Lewy bodies that are positive for the vitamin D-dependent calcium buffering protein, calbindin-D28k and that α-synuclein aggregates are excluded from calbindin-D28k-positive neurons...
February 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28160067/tau-aggregation-influences-cognition-and-hippocampal-atrophy-in-the-absence-of-beta-amyloid-a-clinico-imaging-pathological-study-of-primary-age-related-tauopathy-part
#19
Keith A Josephs, Melissa E Murray, Nirubol Tosakulwong, Jennifer L Whitwell, David S Knopman, Mary M Machulda, Stephen D Weigand, Bradley F Boeve, Kejal Kantarci, Leonard Petrucelli, Val J Lowe, Clifford R Jack, Ronald C Petersen, Joseph E Parisi, Dennis W Dickson
We investigate whether there is any association between the Braak neurofibrillary tangle (NFT) stage and clinical and MRI features in definite primary age-related tauopathy (PART). We analysed 52 cases with a Braak NFT tangle stage >0 and ≤IV, and a Thal phase of 0 (no beta-amyloid present). Twenty-nine (56%) were female. Median age at death was 88 years (IQR 82-92 years). Fifteen (29%) were TDP-positive (75% TDP stage I), 16 (31%) had argyrophilic grain disease and three (6%) had alpha-synuclein-positive Lewy bodies...
February 3, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28159635/%C3%AE-synuclein-binds-to-cytoplasmic-vesicles-in-u251-glioblastoma-cells
#20
Jinyan Duan, Zhengxin Ying, Yang Su, Fankai Lin, Yulin Deng
α-Synuclein is the major component of Lewy bodies, Lewy neurites, and glial cytoplasmic inclusions. It plays an important role in neurodegenerative diseases such as Parkinson's disease, multiple system atrophy, and other synucleinopathies. However, the pathogenesis and neurodegenerative effects of α-synuclein remain unknown. In this study, we established an α-synuclein and an α-synuclein-EGFP overexpressing U251 cell line. α-Synuclein overexpression increases oxidative stress and alters the cell surface and mitochondrial morphologies...
January 31, 2017: Neuroscience Letters
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