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https://www.readbyqxmd.com/read/28228714/narrative-organization-deficit-in-lewy-body-disorders-is-related-to-alzheimer-pathology
#1
Murray Grossman, David J Irwin, Charles Jester, Amy Halpin, Sharon Ash, Katya Rascovsky, Daniel Weintraub, Corey T McMillan
Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28225193/human-neural-progenitor-transplantation-rescues-behavior-and-reduces-%C3%AE-synuclein-in-a-transgenic-model-of-dementia-with-lewy-bodies
#2
Natalie R S Goldberg, Samuel E Marsh, Joseph Ochaba, Brandon C Shelley, Hayk Davtyan, Leslie M Thompson, Joan S Steffan, Clive N Svendsen, Mathew Blurton-Jones
Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α-synuclein (α-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB...
February 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213071/pla2g6-accumulates-in-lewy-bodies-in-park14-and-idiopathic-parkinson-s-disease
#3
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
The histopathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is the occurrence of insoluble fibrillary aggregates known as Lewy bodies, in which phosphorylated α-synuclein (α-syn) is a major component. To date, familial PD-linked gene products, including α-syn, parkin, PINK-1, DJ-1 and LRRK2, are known to be involved in Lewy body formation. Phospholipase A2, group VI (PLA2G6) is the causative gene for PARK14-linked parkinsonism (PARK14), a familial form of juvenile-onset dystonia parkinsonism...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#4
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/28202694/pure-autonomic-failure-predictors-of-conversion-to-clinical-cns-involvement
#5
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/28190674/neuronal-loss-and-%C3%AE-synuclein-pathology-in-the-superior-colliculus-and-its-relationship-to-visual-hallucinations-in-dementia-with-lewy-bodies
#6
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/28177178/association-of-premorbid-personality-with-behavioral-and-psychological-symptoms-in-dementia-with-lewy-bodies-comparison-with-alzheimer-s-disease-patients
#7
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
#8
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
#9
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
#10
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/28166276/homovanillic-acid-and-5-hydroxyindole-acetic-acid-as-biomarkers-for-dementia-with-lewy-bodies-and-coincident-alzheimer-s-disease-an-autopsy-confirmed-study
#11
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/28152401/123i-metaiodobenzylguanidine-myocardial-scintigraphy-with-early-images-alone-is-useful-for-the-differential-diagnosis-of-dementia-with-lewy-bodies
#12
Yuta Manabe, Yoshitaka Inui, Hiroshi Toyama, Kenji Kosaka
123I-metaiodobenzylguanidine cardiac scintigraphy (MIBG) is a useful imaging technique for the diagnosis of dementia with Lewy bodies (DLB). However, MIBG has a serious disadvantage in that it demands a long examination time. The objective of this study was to evaluate statistically the usefulness of the heart/mediastinum ratio (H/M) from the early phase of MIBG for the differential diagnosis of DLB. In total, 113 patients were examined, including 32 non-DLB (19 with Alzheimer's dementia) and 79 DLB patients...
January 20, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28148299/propagation-of-pathological-%C3%AE-synuclein-in-marmoset-brain
#13
Aki Shimozawa, Maiko Ono, Daisuke Takahara, Airi Tarutani, Sei Imura, Masami Masuda-Suzukake, Makoto Higuchi, Kazuhiko Yanai, Shin-Ichi Hisanaga, Masato Hasegawa
α-Synuclein is a defining, key component of Lewy bodies and Lewy neurites in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), as well as glial cytoplasmic inclusions in multiple system atrophy (MSA). The distribution and spreading of these pathologies are closely correlated with disease progression. Recent studies have revealed that intracerebral injection of synthetic α-synuclein fibrils or pathological α-synuclein prepared from DLB or MSA brains into wild-type or transgenic animal brains induced prion-like propagation of phosphorylated α-synuclein pathology...
February 2, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28134631/changes-in-pupil-diameter-are-correlated-with-the-occurrence-of-pareidolias-in-patients-with-dementia-with-lewy-bodies
#14
Yumi Suzuki, Kazumi Hirayama, Tatsuo Shimomura, Makoto Uchiyama, Hiromi Fujii, Etsuro Mori, Yoshiyuki Nishio, Osamu Iizuka, Ryusuke Inoue, Mika Otsuki, Shinya Sakai
Pareidolias are visual illusions of meaningful objects, such as faces and animals, that arise from ambiguous forms embedded in visual scenes. Pareidolias and visual hallucinations have been suggested to have a common underlying neural mechanism in patients with dementia with Lewy bodies (DLB). The aim of the present study was to find an externally observable physiological indicator of pareidolias. Using a pareidolia test developed by Uchiyama and colleagues, we evoked pareidolias in patients with DLB and recorded the resultant changes in the diameters of their pupil...
January 27, 2017: Neuroreport
https://www.readbyqxmd.com/read/28130808/the-usefulness-of-combined-brain-perfusion-single-photon-emission-computed-tomography-dopamine-transporter-single-photon-emission-computed-tomography-and-123-i-metaiodobenzylguanidine-myocardial-scintigraphy-for-the-diagnosis-of-dementia-with-lewy-bodies
#15
Seiju Kobayashi, Kanae Makino, Shigeki Hatakeyama, Takao Ishii, Masaru Tateno, Tomo Iwamoto, Hanako Tsujino, Kazuhito Kawasaki, Kouhei Mikuni, Wataru Ukai, Tomonori Murayama, Eri Hashimoto, Kumiko Utsumi, Chiaki Kawanishi
BACKGROUND: Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT), (123) I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy), and DAT-SPECT...
January 28, 2017: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
https://www.readbyqxmd.com/read/28114455/duration-and-pathologic-correlates-of-lewy-body-disease
#16
Jonathan Graff-Radford, Jeremiah Aakre, Rodolfo Savica, Bradley Boeve, Walter K Kremers, Tanis J Ferman, David T Jones, Kejal Kantarci, David S Knopman, Dennis W Dickson, Walter A Kukull, Ronald C Petersen
Importance: Although patients with dementia with Lewy bodies (DLB) have shorter disease duration than patients with Alzheimer disease dementia, little is known about which factors influence disease duration among patients with DLB. Objective: To identify pathologic correlates of disease duration in participants with Lewy body disease (LBD). Design, Setting, and Participants: This observational study, performed from September 1, 2005, to June 1, 2015, using the National Alzheimer's Coordinating Center database included 807 participants with transitional or diffuse LBD...
January 17, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28088928/multi-modal-mri-investigation-of-volumetric-and-microstructural-changes-in-the-hippocampus-and-its-subfields-in-mild-cognitive-impairment-alzheimer-s-disease-and-dementia-with-lewy-bodies
#17
Elijah Mak, Silvy Gabel, Li Su, Guy B Williams, Robert Arnold, Luca Passamonti, Patricia Vazquez Rodríguez, Ajenthan Surendranathan, W Richard Bevan-Jones, James B Rowe, John T O'Brien
BACKGROUND: Volumetric atrophy and microstructural alterations in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, no study to date has jointly investigated concomitant microstructural and volumetric changes of the hippocampus in dementia with Lewy bodies (DLB). METHODS: A total of 84 subjects (23 MCI, 17 DLB, 14 AD, and 30 healthy controls) were recruited for a multi-modal imaging (3T MRI and DTI) study that included neuropsychological evaluation...
January 16, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28086964/anti-%C3%AE-synuclein-immunotherapy-reduces-%C3%AE-synuclein-propagation-in-the-axon-and-degeneration-in-a-combined-viral-vector-and-transgenic-model-of-synucleinopathy
#18
Brian Spencer, Elvira Valera, Edward Rockenstein, Cassia Overk, Michael Mante, Anthony Adame, Wagner Zago, Peter Seubert, Robin Barbour, Dale Schenk, Dora Games, Robert A Rissman, Eliezer Masliah
Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models...
January 13, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28069058/endosulfine-alpha-inhibits-membrane-induced-%C3%AE-synuclein-aggregation-and-protects-against-%C3%AE-synuclein-neurotoxicity
#19
Daniel Ysselstein, Benjamin Dehay, Isabel M Costantino, George P McCabe, Matthew P Frosch, Julia M George, Erwan Bezard, Jean-Christophe Rochet
Neuropathological and genetic findings suggest that the presynaptic protein α-synuclein (aSyn) is involved in the pathogenesis of synucleinopathy disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. Evidence suggests that the self-assembly of aSyn conformers bound to phospholipid membranes in an aggregation-prone state plays a key role in aSyn neurotoxicity. Accordingly, we hypothesized that protein binding partners of lipid-associated aSyn could inhibit the formation of toxic aSyn oligomers at membrane surfaces...
January 10, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28058207/memory-loss-five-new-things
#20
Ferenc Deak, Nidhi Kapoor, Calin Prodan, Linda A Hershey
PURPOSE OF REVIEW: Memory loss can be due to a wide variety of causes. We provide new information about the biology of common genetic and acquired causes of memory loss in older adults. RECENT FINDINGS: New data are available about the genetics of Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia. Amyloid PET, FDG-PET, and MRI have improved our understanding of how mild cognitive impairment evolves to AD. Several studies have shown links between concussion and chronic traumatic encephalopathy...
December 2016: Neurology. Clinical Practice
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