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https://www.readbyqxmd.com/read/29332010/oligogenic-genetic-variation-of-neurodegenerative-disease-genes-in-980-postmortem-human-brains
#1
Michael J Keogh, Wei Wei, Juvid Aryaman, Ian Wilson, Kevin Talbot, Martin R Turner, Chris-Anne McKenzie, Claire Troakes, Johannes Attems, Colin Smith, Safa Al Sarraj, Chris M Morris, Olaf Ansorge, Stuart Pickering-Brown, Nick Jones, James W Ironside, Patrick F Chinnery
BACKGROUND: Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series. METHODS: We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls...
January 13, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29330884/synapsin-iii-is-a-key-component-of-%C3%AE-synuclein-fibrils-in-lewy-bodies-of-pd-brains
#2
Francesca Longhena, Gaia Faustini, Tatiana Varanita, Michela Zaltieri, Vanessa Porrini, Isabella Tessari, Pietro Luigi Poliani, Cristina Missale, Barbara Borroni, Alessandro Padovani, Luigi Bubacco, Marina Pizzi, PierFranco Spano, Arianna Bellucci
Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III...
January 13, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29327187/does-biochar-affect-the-availability-and-chemical-fractionation-of-phosphate-in-soils
#3
Can Hong, Shenggao Lu
Biochar as a soil amendment has been reported to affect the content and availability of soil nutrients. In this study, we aimed to test whether the biochar addition to soils would change the availability and chemical fractionation of phosphate in soils. Two soils (Ultisol and Alfisol) were amended with five kinds of biochars at application rate of 0, 1, and 2% (w/w). After 3-month incubation, availability and chemical forms of P were measured to investigate the potential effect and role of biochar in improving P availability in soils...
January 11, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29321140/cerebrospinal-fluid-alzheimer-biomarkers-can-be-useful-for-discriminating-dementia-with-lewy-bodies-from-alzheimer-s-disease-at-the-prodromal-stage
#4
Olivier Bousiges, Stephanie Bombois, Susanna Schraen, David Wallon, Muriel Muraine Quillard, Audrey Gabelle, Sylvain Lehmann, Claire Paquet, Elodie Amar-Bouaziz, Eloi Magnin, Carole Miguet-Alfonsi, Xavier Delbeuck, Thomas Lavaux, Pierre Anthony, Nathalie Philippi, Frederic Blanc
BACKGROUND: Differential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is not straightforward, especially in the early stages of disease. We compared AD biomarkers (phospho-Tau181, total-Tau, Aβ42 and Aβ40) in cerebrospinal fluid (CSF) of patients with DLB and AD, focusing especially on the prodromal stage. METHODS: A total of 1221 CSF were collected in different memory centres (ePLM network) in France and analysed retrospectively...
January 10, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29310663/%C3%AE-synuclein-accumulation-and-gba-deficiency-due-to-l444p-gba-mutation-contributes-to-mptp-induced-parkinsonism
#5
Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L Dawson, Ted M Dawson, Yunjong Lee, Han Seok Ko
BACKGROUND: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin...
January 8, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29305919/pathological-role-of-lipid-interaction-with-%C3%AE-synuclein-in-parkinson-s-disease
#6
REVIEW
Mari Suzuki, Kazunori Sango, Keiji Wada, Yoshitaka Nagai
Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In sporadic PD and DLB, normally harmless αSyn proteins without any mutations might gain toxic functions by unknown mechanisms. Thus, it is important to elucidate the factors promoting the toxic conversion of αSyn, towards understanding the pathogenesis of and developing disease-modifying therapies for PD and DLB. Accumulating biophysical and biochemical studies have demonstrated that αSyn interacts with lipid membrane, and the interaction influences αSyn oligomerization and aggregation...
January 3, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29305061/a-refined-concept-%C3%AE-synuclein-dysregulation-disease
#7
REVIEW
Hideki Mochizuki, Chi-Jing Choong, Eliezer Masliah
α-synuclein (αSyn) still remains a mysterious protein even two decades after SNCA encoding it was identified as the first causative gene of familial Parkinson's disease (PD). Accumulation of αSyn causes α-synucleinopathies including PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent advances in therapeutic approaches offer new antibody-, vaccine-, antisense-oligonucleotide- and small molecule-based options to reduce αSyn protein levels and aggregates in patient's brain. Gathering research information of other neurological disease particularly Alzheimer's disease, recent disappointment of an experimental amyloid plaques busting antibody in clinical trials underscores the difficulty of treating people who show even mild dementia as damage in their brain may already be too extensive...
January 2, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29282408/behavioural-and-psychological-symptoms-of-dementia-correlates-and-impact-on-caregiver-distress
#8
Adreesh Mukherjee, Atanu Biswas, Arijit Roy, Samar Biswas, Goutam Gangopadhyay, Shyamal Kumar Das
Aims: To evaluate the behavioural and psychological symptoms of dementia (BPSD), to determine their correlation with types and stages of dementia and patient demographics, and to assess the impact on caregiver distress. Methods: This cross-sectional study recruited consecutive dementia patients and caregivers who attended our cognitive clinic. Standard criteria were used to classify types of dementia. BPSD were assessed with the Neuropsychiatric Inventory, and its distress scale was used for caregiver distress...
September 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/29278715/accumulation-of-beta-synuclein-in-cortical-neurons-is-associated-with-autophagy-attenuation-in-the-brains-of-dementia-with-lewy-body-patients
#9
Tracey Evans, Wai Ling Kok, Katrina Cowan, Megan Hefford, Oleg Anichtchik
Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia, where an accumulation of aggregated fibrillar alpha-synuclein in neurons of limbic and forebrain regions of the brain leads to visual hallucination, cognitive impairment of a fluctuating nature and extrapyramidal motor disturbances. Beta-synuclein counteracts aggregation of alpha-synuclein in vitro and in animal models, however it is not clear whether this effect occurs in human Lewy body dementia (LBD) diseases. Here we examine expression of alpha-, beta-synuclein and autophagy markers in the frontal cortex (BA9) and occipital cortex (BA18-19) of patients with neuropathologically confirmed DLB/LBD and age-matched controls...
December 23, 2017: Brain Research
https://www.readbyqxmd.com/read/29261640/the-added-value-of-dynamic-18f-florbetapir-pet-in-the-assessment-of-dementia-with-lewy-bodies
#10
Diego Alfonso López Mora, Valle Camacho, Alberto Lleó, Alejandro Fernández, Ignasi Carrió
Dementia with Lewy bodies (DLB) is the most common cause of dementia after Alzheimer disease. It is often underdiagnosed because of the overlapping with Alzheimer disease symptoms. We report the F-FDG and F-florbetapir dynamic PET images (early and delay phases) of an 83-year-old woman with cognitive impairment associated with visual hallucinations and parkinsonism due to probable DLB. This image highlights that the early phases of F-florbetapir may reflect regional cerebral perfusion with a pattern very similar to that of regional glucose metabolism in DLB...
December 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29260408/practical-treatment-of-lewy-body-disease-in-the-clinic-patient-and-physician-perspectives
#11
Elisabet Londos
This article describes the practical considerations in the clinical medical treatment in dementia with Lewy body (DLB) patients. It is illustrated with the voice of a DLB sufferer and his wife. According to our experience, emanating from a 15 year collaboration between a doctor and a nurse at a memory clinic, there are several possible therapeutical entrances. However, the order in which the medication is introduced is of great importance to avoid aggravation of other DLB symptoms. We start the treatment with cholinesterase inhibitor and memantine, and; thereafter, we treat the most disturbing symptom...
December 19, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/29248892/peripheral-inflammation-in-prodromal-alzheimer-s-and-lewy-body-dementias
#12
Eleanor King, John Tiernan O'Brien, Paul Donaghy, Christopher Morris, Nicola Barnett, Kirsty Olsen, Carmen Martin-Ruiz, John-Paul Taylor, Alan J Thomas
OBJECTIVES: There is growing evidence for the role of systemic inflammation in Alzheimer's disease (AD) and other neurodegenerative diseases; however the systemic inflammatory profile in dementia with Lewy bodies (DLB) has never before been investigated. This study aimed to characterise systemic inflammatory mediators in established DLB and AD, as well as in their prodromal, mild cognitive impairment (MCI) phases. METHODS: We obtained plasma samples from patients with DLB (n=37), AD (n=20), MCI with DLB profile (n=38), MCI with AD profile (n=20) and healthy control subjects (n=20)...
December 16, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29246926/combined-active-humoral-and-cellular-immunization-approaches-for-the-treatment-of-synucleinopathies
#13
Edward Rockenstein, Gary Ostroff, Fusun Dikengil, Florentina Rus, Michael Mante, Jazmin Florio, Anthony Adame, Ivy Trinh, Changyoun Kim, Cassia Overk, Eliezer Masliah, Robert A Rissman
Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and Multiple System Atrophy (MSA) are age-related neurodegenerative disorders characterized by progressive accumulation of α-synuclein (α-syn) and jointly termed synucleinopathies. Currently, no disease-modifying treatments are available for these disorders. Previous preclinical studies showed that active and passive immunizations targeting α-syn partially ameliorates behavioral deficits and α-syn accumulation; however, it is unknown if combining humoral and cellular immunization might act synergistically to reduce inflammation and improve microglial-mediated α-syn clearance...
December 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29246765/fkbp12-immunopositive-inclusions-in-patients-with-%C3%AE-synucleinopathies
#14
Yasuyuki Honjo, Takashi Ayaki, Tomohisa Horibe, Hidefumi Ito, Ryosuke Takahashi, Koji Kawakami
α-Synuclein (α-SYN), a presynaptic protein with the tendency to aggregate, is linked to α-synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). α-SYN is the main component of round intracytoplasmic inclusions called Lewy bodies (LBs), which are the hallmark of PD and DLB. In addition, accumulation of amyloid-β and neurofibrillary tangles as in the pathology of Alzheimer's disease has been found in the DLB brain. Glial cytoplasmic inclusions are an MSA-specific type of inclusion found in oligodendrocytes and mainly comprise α-SYN...
December 12, 2017: Brain Research
https://www.readbyqxmd.com/read/29222591/dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-current-concepts-and-controversies
#15
REVIEW
Kurt A Jellinger
Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD), although sharing many clinical, neurochemical and morphological features, according to DSM-5, are two entities of major neurocognitive disorders with Lewy bodies of unknown etiology. Despite considerable clinical overlap, their diagnosis is based on an arbitrary distinction between the time of onset of motor and cognitive symptoms: dementia often preceding parkinsonism in DLB and onset of cognitive impairment after onset of motor symptoms in PDD...
December 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29198173/autophagy-inhibition-promotes-snca-alpha-synuclein-release-and-transfer-via-extracellular-vesicles-with-a-hybrid-autophagosome-exosome-like-phenotype
#16
Georgia Minakaki, Stefanie Menges, Agnes Kittel, Evangelia Emmanouilidou, Iris Schaeffner, Katalin Barkovits, Anna Bergmann, Edward Rockenstein, Anthony Adame, Franz Marxreiter, Brit Mollenhauer, Douglas Galasko, Edit Irén Buzás, Ursula Schlötzer-Schrehardt, Katrin Marcus, Wei Xiang, Dieter Chichung Lie, Kostas Vekrellis, Eliezer Masliah, Jürgen Winkler, Jochen Klucken
The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease and dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but the underlying cellular mechanisms are not well understood. Several studies identified SNCA in exosome/extracellular vesicle (EV) fractions. EVs are generated in the multivesicular body compartment and either released upon its fusion with the plasma membrane, or cleared via the ALP...
December 4, 2017: Autophagy
https://www.readbyqxmd.com/read/29195744/discrimination-of-atypical-parkinsonisms-with-transcranial-magnetic-stimulation
#17
Alberto Benussi, Valentina Dell'Era, Valentina Cantoni, Clarissa Ferrari, Salvatore Caratozzolo, Luca Rozzini, Antonella Alberici, Alessandro Padovani, Barbara Borroni
BACKGROUND: Differential diagnosis of atypical parkinsonian disorders, i.e. dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS) still remains problematic. Furthermore, DLB may overlap with Alzheimer's disease (AD) in the early stages of disease. OBJECTIVE: To determine whether transcranial magnetic stimulation (TMS) can be used to classify atypical parkinsonian disorders and AD. METHODS: A paired-pulse TMS multi-paradigm approach assessing multiple intracortical circuits, as short interval intracortical inhibition-facilitation and short latency afferent inhibition, was used to model a decision tree analysis and determine diagnostic accuracy in classifying different neurodegenerative disorders...
November 22, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/29193464/functional-connectivity-in-dementia-with-lewy-bodies-a-within-and-between-network-analysis
#18
Julia Schumacher, Luis R Peraza, Michael Firbank, Alan J Thomas, Marcus Kaiser, Peter Gallagher, John T O'Brien, Andrew M Blamire, John-Paul Taylor
Dementia with Lewy bodies (DLB) is a common form of dementia and is characterized by cognitive fluctuations, visual hallucinations, and Parkinsonism. The phenotypic expression of the disease may, in part, relate to alterations in functional connectivity within and between brain networks. This resting-state study sought to clarify this in DLB, how networks differed from Alzheimer's disease (AD), and whether they were related to clinical symptoms in DLB. Resting-state networks were estimated using independent component analysis...
November 29, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/29187334/cognitive-profile-in-prodromal-disease-dementia-with-lewy-bodies
#19
Jennifer Kemp, Nathalie Philippi, Clélie Phillipps, Anne Botzung, Frédéric Blanc
This paper reviews findings on cognition in prodromal dementia with Lewy bodies (DLB). The issue of differential diagnosis between DLB and Alzheimer's disease (AD) on the one hand, and Parkinson's disease (PD) on the other hand, at prodromal stages of the diseases is discussed. The cognitive profile of prodromal DLB is also evaluated in terms of cognitive deficits and « cognitive weaknesses » (low performances although in normal range). Findings suggest that visuo-constructive tests and verbal fluency are particularly relevant to dfferentiate DLB from AD...
December 1, 2017: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
https://www.readbyqxmd.com/read/29164600/18f-pet-with-florbetaben-for-the-early-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#20
REVIEW
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Leon Flicker, Xavier Bonfill Cosp
BACKGROUND: 18F-florbetaben uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like 18F-florbetaben...
November 22, 2017: Cochrane Database of Systematic Reviews
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