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lewy body dementia and Parkinson's

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https://www.readbyqxmd.com/read/29656189/quantitative-electroencephalography-as-a-marker-of-cognitive-fluctuations-in-dementia-with-lewy-bodies-and-an-aid-to-differential-diagnosis
#1
Myrto Stylianou, Nicholas Murphy, Luis R Peraza, Sara Graziadio, Ruth Cromarty, Alison Killen, John T O' Brien, Alan J Thomas, Fiona E N LeBeau, John-Paul Taylor
OBJECTIVE: We investigated for quantitative EEG (QEEG) differences between Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) patients and healthy controls, and for QEEG signatures of cognitive fluctuations (CFs) in DLB. METHODS: We analysed eyes-closed, resting state EEGs from 18 AD, 17 DLB and 17 PDD patients with mild dementia, and 21 age-matched controls. Measures included spectral power, dominant frequency (DF), frequency prevalence (FP), and temporal DF variability (DFV), within defined EEG frequency bands and cortical regions...
April 3, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29629495/lewy-body-disease-clinical-and-pathological-overlap-syndrome-between-synucleinopathies-parkinson-disease-and-tauopathies-alzheimer-disease
#2
REVIEW
Clovis Foguem, Patrick Manckoundia
Lewy body disease (LBD) is a neurodegenerative disease resulting in dementia. It shares clinical and pathological features with Parkinson disease (PD), the most frequent synucleinopathy, Parkinson disease dementia (PDD), and Alzheimer disease (AD), a tauopathy. Even though the diagnostic criteria for these neurodegenerative diseases are clearly established, and recently revised for LBD, their precise clinical diagnosis is often difficult because LBD, PD, PDD, and AD share epidemiological, clinical, and pathological characteristics...
April 8, 2018: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/29624752/biomarkers-for-cognitive-impairment-in-lewy-body-disorders-status-and-relevance-for-clinical-trials
#3
REVIEW
Andrew Siderowf, Dag Aarsland, Brit Mollenhauer, Jennifer G Goldman, Bernard Ravina
Biomarkers have the potential to improve diagnosis and prognosis, and guide clinical treatment decisions. In research, biomarkers can be used for patient selection and as outcome measures in clinical trials. A range of biochemical and imaging biomarkers are relevant to patients with Lewy body disorders, including PD, PD dementia, and dementia with Lewy bodies. Dopaminergic imaging is used for differential diagnosis of parkinsonian disorders versus tremor disorders without dopamingeric deficits, and also to differentiate dementia with Lewy bodies from Alzheimer's disease...
April 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29623065/-in-situ-proximity-ligation-assay-reveals-co-localization-of-alpha-synuclein-and-snare-proteins-in-murine-primary-neurons
#4
Leire Almandoz-Gil, Emma Persson, Veronica Lindström, Martin Ingelsson, Anna Erlandsson, Joakim Bergström
The aggregation of alpha-synuclein (αSyn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of αSyn is to promote the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between αSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA)...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29621183/tau-induced-pathology-in-epilepsy-and-dementia-notions-from-patients-and-animal-models
#5
REVIEW
Marina P Sánchez, Ana M García-Cabrero, Gentzane Sánchez-Elexpuru, Daniel F Burgos, José M Serratosa
Patients with dementia present epilepsy more frequently than the general population. Seizures are more common in patients with Alzheimer's disease (AD), dementia with Lewy bodies (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) than in other dementias. Missense mutations in the microtubule associated protein tau (MAPT) gene have been found to cause familial FTD and PSP, while the P301S mutation in MAPT has been associated with early-onset fast progressive dementia and the presence of seizures...
April 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29619853/multi-modality-molecular-imaging-characteristics-of-dementia-with-lewy-bodies
#6
Zhong-Bao Gao, Wei Wang, Xing-Li Zhao, Tong Chen, Li-Ping Fu, Bai-Xuan Xu, Zhen-Fu Wang
Objective Dementia with Lewy bodies (DLB) is a common type of neurodegenerative dementia. Molecular neuroimaging using dopamine transporter (DaT), Pittsburgh compound B (PIB), and fluorodeoxyglucose (FDG) positron emission tomography (PET) has advantages in detecting dopaminergic neuron loss, abnormal amyloid β-protein deposition, and glucose metabolism changes in patients with neurodegenerative disorders. However, the multi-modality molecular imaging features of patients with DLB have rarely been reported...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29617933/a-qualitative-study-of-female-caregiving-spouses-experiences-of-intimate-relationships-as-cognition-declines-in-parkinson-s-disease
#7
Sabina Vatter, Kathryn R McDonald, Emma Stanmore, Linda Clare, Sheree A McCormick, Iracema Leroi
Background: the complex and progressive nature of Parkinson's disease (PD) and cognitive impairment may necessitate a care provider, a role which is frequently undertaken by a spouse. Providing and receiving care related to dementia impacts on a couple's partnership and may result in decreased intimacy and relationship satisfaction. Objective: to explore the changes in long-term intimate relationships in Parkinson's-related dementia, as perceived by spouses providing care to their partners...
April 3, 2018: Age and Ageing
https://www.readbyqxmd.com/read/29608598/sequestration-of-synaptic-proteins-by-alpha-synuclein-aggregates-leading-to-neurotoxicity-is-inhibited-by-small-peptide
#8
Mal-Gi Choi, Mi Jin Kim, Do-Geun Kim, Ri Yu, You-Na Jang, Won-Jong Oh
α-Synuclein (α-syn) is a major component of Lewy bodies found in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Under the pathological conditions, α-syn tends to generate a diverse form of aggregates showing toxicity to neuronal cells and able to transmit across cells. However, mechanisms by which α-syn aggregates affect cytotoxicity in neurons have not been fully elucidated. Here we report that α-syn aggregates preferentially sequester specific synaptic proteins such as vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 (SNAP25) through direct binding which is resistant to SDS...
2018: PloS One
https://www.readbyqxmd.com/read/29602778/clinical-imaging-in-dementia-with-lewy-bodies
#9
REVIEW
Ajenthan Surendranathan, John Tiernan O'Brien
Dementia with Lewy bodies (DLB) is a common neurodegenerative dementia in older people; however, the clinical features, particularly cognitive fluctuations and rapid eye movement sleep disorder, are often hard to elicit, leading to difficulty in making the diagnosis clinically. Here we examine the literature for the evidence behind imaging modalities that could assist in making the diagnosis. Dopamine transporter (DAT) imaging remains the best modality for differentiation from dementia of Alzheimer's type with high sensitivity and specificity reported based on pathological diagnoses...
March 29, 2018: Evidence-based Mental Health
https://www.readbyqxmd.com/read/29599149/alpha-synuclein-aggregates-activate-calcium-pump-serca-leading-to-calcium-dysregulation
#10
Cristine Betzer, Louise Berkhoudt Lassen, Anders Olsen, Rikke Hahn Kofoed, Lasse Reimer, Emil Gregersen, Jin Zheng, Tito Calì, Wei-Ping Gai, Tong Chen, Arne Moeller, Marisa Brini, Yuhong Fu, Glenda Halliday, Tomasz Brudek, Susana Aznar, Bente Pakkenberg, Jens Peter Andersen, Poul Henning Jensen
Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca2+ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca2+ levels followed by a later Ca2+ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro , and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca2+ CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis elegans in vivo Proximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies...
March 29, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29595653/type-i-gaucher-disease-with-bullous-pemphigoid-and-parkinson-disease-a-case-report
#11
Damien Le Peillet, Virginie Prendki, Véronique Trombert, Emmanuel Laffitte, Frédéric Assal, Jean Luc Reny, Christine Serratrice
RATIONALE: Gaucher disease (GD) is a rare genetic lysosomal storage disorder inherited in an autosomal recessive pattern. GD is due to the deficiency of a lysosomal enzyme, acid beta-glucosidase (or glucocerebrosidase). Type 1 Gaucher disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen, and liver as well as bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts, and avascular necrosis leading to degenerative arthropathy)...
March 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29593630/parkinson-s-disease-dementia-and-dementia-with-lewy-bodies-have-similar-neuropsychological-profiles
#12
Georgina M Aldridge, Allison Birnschein, Natalie L Denburg, Nandakumar S Narayanan
Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are common causes of dementia worldwide. Although considered separate entities based on the relative temporal onset of motor symptoms vs. diagnosis of dementia, it is unknown if these diseases truly have distinct cognitive profiles. We hypothesized that patients divided into PDD and DLB categories strictly by temporal criteria would have different neuropsychological profiles. We investigated this question via neuropsychological testing of PDD and DLB patients at the University of Iowa...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29589283/detecting-alpha-synuclein-seeding-activity-in-formaldehyde-fixed-msa-patient-tissue-by-pmca
#13
Katelyn Becker, Xinhe Wang, Kayla Vander Stel, Yaping Chu, Jeffrey Kordower, Jiyan Ma
Alpha synuclein (α-syn) is central to the pathogenesis of a group of neurodegenerative disorders known as synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Aggregation of α-syn is the pathologic hallmark of these disorders and is intimately associated with the pathogenic changes. The prion-like hypothesis postulates that the aggregated α-syn provides a template to seed the aggregation of normal α-syn and spread the pathology. Thus far, it remains unclear whether aggregated α-syn can be a useful biomarker for diagnosis and/or tracking disease progression, which is mainly due to the lack of a suitable biochemical assay...
March 27, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29579237/acid-ceramidase-inhibition-ameliorates-%C3%AE-synuclein-accumulation-upon-loss-of-gba1-function
#14
Myung Jong Kim, Sohee Jeon, Lena F Burbulla, Dimitri Krainc
GBA1 encodes the lysosomal enzyme β-glucocerebrosidase (GCase) which converts glucosylceramide into ceramide and glucose. Mutations in GBA1 lead to Gaucher's disease and are a major risk factor for Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), synucleinopathies characterized by accumulation of intracellular α-synuclein. In this study, we examined whether decreased ceramide that is observed in GCase-deficient cells contributes to α-synuclein accumulation. We demonstrated that deficiency of GCase leads to a reduction of C18-ceramide species and altered intracellular localization of Rab8a, a small GTPase implicated in secretory autophagy, that contributed to impaired secretion of α-synuclein and accumulation of intracellular α-synuclein...
March 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29578489/rem-sleep-behavior-disorder-and-alzheimer-s-disease-definitely-no-relationship
#15
Andrea Galbiati, Giulia Carli, Michael Hensley, Luigi Ferini-Strambi
Rapid eye movement (REM) sleep behavior disorder (RBD) is a REM sleep parasomnia characterized by the loss of the typical muscular atonia present during healthy REM sleep. RBD can occur in the absence of other neurological conditions or in association with a neurodegenerative disorder. It is now well established that RBD is a strong predictor of neurodegeneration, in particular synucleinopathies, such as Parkinson's disease, Lewy body dementia (LBD), or multiple system atrophy. However, some longitudinal studies report that a minority of patients develop either overlapping form of dementia or Alzheimer disease's (AD)...
March 23, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29576439/lrrk2-protective-haplotype-and-full-sequencing-study-in-rem-sleep-behavior-disorder
#16
Bouchra Ouled Amar Bencheikh, Jennifer A Ruskey, Isabelle Arnulf, Yves Dauvilliers, Christelle Charley Monaca, Valérie Cochen De Cock, Jean-François Gagnon, Dan Spiegelman, Michele T M Hu, Birgit Högl, Ambra Stefani, Luigi Ferini-Strambi, Giuseppe Plazzi, Elena Antelmi, Peter Young, Anna Heidbreder, Brit Mollenhauer, Friederike Sixel-Döring, Claudia Trenkwalder, Wolfgang Oertel, Jacques Y Montplaisir, Ronald B Postuma, Guy A Rouleau, Ziv Gan-Or
BACKGROUND: Individuals with rapid eye movement (REM)-sleep behavior disorder (RBD) are likely to progress to synucleinopathies, mainly Parkinson's disease (PD), dementia with Lewy-bodies (DLB) and multiple system atrophy (MSA). The genetics of RBD only partially overlaps with PD and DLB, and the role of LRRK2 variants in risk for RBD is still not clear. METHODS: The full coding sequence, exon-intron boundaries and 5' and 3' untranslated regions of LRRK2 were sequenced using targeted next-generation sequencing...
March 21, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29570843/molecular-changes-in-the-absence-of-severe-pathology-in-the-pulvinar-in-dementia-with-lewy-bodies
#17
Daniel Erskine, Jinhui Ding, Alan J Thomas, Alice Kaganovich, Ahmad A Khundakar, Peter S Hanson, John-Paul Taylor, Ian G McKeith, Johannes Attems, Mark R Cookson, Christopher M Morris
BACKGROUND: Dementia with Lewy bodies is characterized by transient clinical features, including fluctuating cognition and visual hallucinations, implicating dysfunction of cerebral hub regions, such as the pulvinar nuclei of the thalamus. However, the pulvinar is typically only mildly affected by Lewy body pathology in dementia with Lewy bodies, suggesting additional factors may account for its proposed dysfunction. METHODS: We conducted a comprehensive analysis of postmortem pulvinar tissue using whole-transcriptome RNA sequencing, protein expression analysis, and histological evaluation...
March 23, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29570792/genomics-studies-on-musical-aptitude-music-perception-and-practice
#18
REVIEW
Irma Järvelä
When searching for genetic markers inherited together with musical aptitude, genes affecting inner ear development and brain function were identified. The alpha-synuclein gene (SNCA), located in the most significant linkage region of musical aptitude, was overexpressed when listening and performing music. The GATA-binding protein 2 gene (GATA2) was located in the best associated region of musical aptitude and regulates SNCA in dopaminergic neurons, thus linking DNA- and RNA-based studies of music-related traits together...
March 23, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29569570/behavioral-and-psychological-symptoms-in-lewy-body-disease-a-review
#19
Lucie Jurek, Mathieu Herrmann, Mathilde Bonze, Sophie Brunet, Catherine Padovan, Jean-Michel Dorey
Dementia with Lewy bodies (DLB) is a common neurodegenerative disease, second in terms of prevalence after Alzheimer's disease (AD). DLB may be suspected according to three core features which are cognitive and motor fluctuations, early visual hallucinations and parkinsonism; and more recently, according to the new criteria, REM sleep behavior disorder (RBD). Behavorial and psychological symptoms associated with DLB are more frequent, more severe and appear earlier than those found in other neurodegenerative diseases...
March 1, 2018: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
https://www.readbyqxmd.com/read/29563864/pathophysiological-consequences-of-neuronal-%C3%AE-synuclein-overexpression-impacts-on-ion-homeostasis-stress-signaling-mitochondrial-integrity-and-electrical-activity
#20
Johan Tolö, Grit Taschenberger, Kristian Leite, Markus A Stahlberg, Gesche Spehlbrink, Janina Kues, Francesca Munari, Stefano Capaldi, Stefan Becker, Markus Zweckstetter, Camin Dean, Mathias Bähr, Sebastian Kügler
α-Synuclein (α-Syn) is intimately linked to the etiology of Parkinson's Disease, as mutations and even subtle increases in gene dosage result in early onset of the disease. However, how this protein causes neuronal dysfunction and neurodegeneration is incompletely understood. We thus examined a comprehensive range of physiological parameters in cultured rat primary neurons overexpressing α-Syn at levels causing a slowly progressive neurodegeneration. In contradiction to earlier reports from non-neuronal assay systems we demonstrate that α-Syn does not interfere with essential ion handling capacities, mitochondrial capability of ATP production or basic electro-physiological properties like resting membrane potential or the general ability to generate action potentials...
2018: Frontiers in Molecular Neuroscience
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