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Hitoshi Takahashi - One of the best experts on this subject based on the ideXlab platform.
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alteration of autophagosomal proteins lc3 gabarap and gate 16 in Lewy Body disease
Neurobiology of Disease, 2011Co-Authors: Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi WakabayashiAbstract:Macroautophagy is a dynamic process whereby cytoplasmic molecules are sequestered within autophagosomes. Based on amino acid similarity, there exist two groups of mammalian autophagy-related gene (Atg) 8 homologues [microtubule-associated protein 1 light chain 3 (LC3) and γ-aminobutyric-acid type A receptor associated proteins (GABARAPs)], which play essential role in autophagosomal formation. Despite recent progress in studies on LC3, the other Atg8 homologues remain to be poorly understood, especially in pathological condition. In this study, we determined whether Atg8 homologues are affected in Lewy Body disease, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Our findings indicated that biochemical and pathological properties of LC3 were altered and that the level of LC3 was increased in an insoluble fraction from the brain of patients with DLB, whereas the level of GABARAPs was decreased in DLB. Furthermore, immunohistochemical staining revealed that both LC3 and GABARAPs were localized in Lewy bodies in PD and DLB. These findings suggest that autophagic function is impaired through alteration of Atg8 homologues in Lewy Body disease.
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Proteinase K-resistant alpha-synuclein is deposited in presynapses in human Lewy Body disease and A53T alpha-synuclein transgenic mice.
Acta neuropathologica, 2010Co-Authors: Kunikazu Tanji, Fumiaki Mori, Junsei Mimura, Ken Itoh, Akiyoshi Kakita, Hitoshi Takahashi, Koichi WakabayashiAbstract:Abnormally modified alpha-synuclein is a pathological hallmark of Parkinson's disease and the other alpha-synucleinopathies. Since proteinase K (PK) treatment is known to enhance the immunoreactivity of abnormal alpha-synuclein, we immunohistochemically examined the brain of transgenic (Tg) mice expressing human mutant A53T alpha-synuclein using this retrieval method. PK treatment abolished the immunoreactivity of alpha-synuclein in abnormal inclusions as well as of endogenous alpha-synuclein in Tg mice, whereas PK-resistant alpha-synuclein was found in the presynaptic nerve terminals, especially in the hippocampus and temporal cortex. In human Lewy Body disease, PK-resistant alpha-synuclein was deposited in Lewy bodies and Lewy neurites, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Biochemical analysis revealed that PK-resistant alpha-synuclein was detected in the presynaptic fraction in Tg mice and human Lewy Body disease. Although PK-resistant alpha-synuclein was found in the presynapse in Tg mice even at 1 week of age, it was not phosphorylated until at least 8 months of age. Moreover, PK-resistant alpha-synuclein in the presynapse was not phosphorylated in human Lewy Body disease. These findings suggest that phosphorylation is not necessary to cause the conversion of soluble form to PK-resistant alpha-synuclein. Considering that native alpha-synuclein is a soluble protein localized to the presynaptic terminals, our findings suggest that PK-resistant alpha-synuclein may disturb the neurotransmission in alpha-synucleinopathies.
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cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy Body disease
Acta Neuropathologica, 2005Co-Authors: Satoshi Orimo, Fumiaki Mori, Koichi Wakabayashi, Takeshi Amino, Yoshinori Itoh, Atsushi Takahashi, Tohru Kojo, Toshiki Uchihara, Kuniaki Tsuchiya, Hitoshi TakahashiAbstract:Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I]MIBG myocardial scintigraphy has been reported in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We hypothesized that cardiac sympathetic denervation might account for the pathomechanism. To elucidate the extent, frequency and pattern of cardiac sympathetic nerve involvement in Lewy Body disease and related neurodegenerative disorders, we immunohistochemically examined heart tissues from patients with PD (n=11), DLB (n=7), DLB with Alzheimer’s disease (DLB/AD; n=4), multiple system atrophy (MSA; n=8), progressive supranuclear palsy (PSP; n=5), pure AD (n=10) and control subjects (n=5) together with sympathetic ganglia from patients with PD (n=5) and control subjects (n=4), using an antiBody against tyrosine hydroxylase (TH). TH-immunoreactive nerve fibers in the hearts had almost entirely disappeared in nearly all the patients with PD, DLB and DLB/AD, whereas they were well preserved in all the patients with PSP and pure AD as well as in all except for one patient with MSA. In PD, neurons in the sympathetic ganglia were preserved in all except for one patient. Decreased cardiac uptake of MIBG in Lewy Body disease reflects actual cardiac sympathetic denervation, which precedes the neuronal loss in the sympathetic ganglia.
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Lewy Body type degeneration in cardiac plexus in parkinson s and incidental Lewy Body diseases
Neurology, 1999Co-Authors: K Iwanaga, Koichi Wakabayashi, M Yoshimoto, Itsuro Tomita, Hideyo Satoh, H Takashima, Akira Satoh, Makiko Seto, Mitsuhiro Tsujihata, Hitoshi TakahashiAbstract:Article abstract Heart tissues of patients with PD or incidental Lewy Body (LB) disease (ILBD) were examined by light and electron microscopy. LBs and α-synuclein–positive neurites were identified in the hearts from 9 of 11 patients with PD and from 7 of 7 patients with ILBD. LBs were present in both tyrosine hydroxylase-positive and -negative nerve processes, which are nerves of extrinsic sympathetic and intrinsic origin, respectively. These findings provide histologic evidence that the postganglionic sympathetic and intrinsic neurons in the heart are involved in the PD disease process.
James E Galvin - One of the best experts on this subject based on the ideXlab platform.
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Lewy Body dementia association s industry advisory council proceedings of the second annual meeting
Alzheimer's Research & Therapy, 2021Co-Authors: Jennifer G. Goldman, Bradley F. Boeve, David J. Irwin, James E Galvin, Melissa J. Armstrong, Doug R. Galasko, James B. Leverenz, Karen Marder, Victor Abler, Kevin BiglanAbstract:In 2019, the Lewy Body Dementia Association formed an Industry Advisory Council to bring together a collaborative group of stakeholders with the goal of accelerating clinical research into Lewy Body dementia treatments. At the second annual meeting of the Industry Advisory Council, held virtually on June 18, 2020, the key members presented ongoing and planned efforts toward the council's goals. The meeting also featured a discussion about the effects of the COVID-19 pandemic on Lewy Body dementia clinical research, lessons learned from that experience, and how those lessons can be applied to the design and conduct of future clinical trials. This report provides a brief summary of the meeting proceedings with a focus on efforts to improve and adapt future Lewy Body dementia clinical research.
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Lewy Body Dementia Association’s Industry Advisory Council: proceedings of the second annual meeting
'Springer Science and Business Media LLC', 2021Co-Authors: Jennifer G. Goldman, Bradley F. Boeve, David J. Irwin, James E Galvin, Melissa J. Armstrong, Doug R. Galasko, James B. Leverenz, Karen Marder, Victor Abler, Kevin BiglanAbstract:Abstract In 2019, the Lewy Body Dementia Association formed an Industry Advisory Council to bring together a collaborative group of stakeholders with the goal of accelerating clinical research into Lewy Body dementia treatments. At the second annual meeting of the Industry Advisory Council, held virtually on June 18, 2020, the key members presented ongoing and planned efforts toward the council’s goals. The meeting also featured a discussion about the effects of the COVID-19 pandemic on Lewy Body dementia clinical research, lessons learned from that experience, and how those lessons can be applied to the design and conduct of future clinical trials. This report provides a brief summary of the meeting proceedings with a focus on efforts to improve and adapt future Lewy Body dementia clinical research
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Lewy Body dementia association s research centers of excellence program inaugural meeting proceedings
Alzheimer's Research & Therapy, 2019Co-Authors: Bethany Peterson, David J. Irwin, James E Galvin, Daniel I Kaufer, Jennifer G. Goldman, Melissa J. Armstrong, James B. Leverenz, Douglas Galasko, Henry L Paulson, Angela LundeAbstract:The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator’s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy Body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics.
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improving the clinical detection of Lewy Body dementia with the Lewy Body composite risk score
Alzheimer's & Dementia: Diagnosis Assessment & Disease Monitoring, 2015Co-Authors: James E GalvinAbstract:Abstract Introduction Dementia with Lewy bodies (DLB) is a challenge to diagnose, particularly outside of expert centers with long delays in diagnosis leading to significant burden to patients and caregivers. Although consensus criteria have excellent specificity, there is no standardized way to assess symptoms reducing sensitivity. We developed the Lewy Body composite risk score (LBCRS) from autopsy-verified cases to improve the ability to detect DLB in clinic and research populations. Methods The LBCRS was tested in a consecutive series of 256 patients compared with the clinical dementia rating and gold standard measures of cognition, motor symptoms, function, and behavior. Psychometric properties including floor and ceiling effects; concurrent, construct, and known-groups validity; and internal consistency of the LBCRS were determined. Receiver operator characteristic (ROC) curves assessed the ability of LBCRS to differentiate (1) DLB from Alzheimer's disease (AD), (b) DLB from all dementia, and (c) mild cognitive impairment (MCI) due to DLB from MCI due to AD. The LBCRS was completed independent of the clinical evaluation. Results Mean LBCRS scores were significantly different between DLB and AD (6.1 ± 2.0 vs. 2.4 ± 1.3, P P Discussion The LBCRS increases diagnostic probability that Lewy Body pathology is contributing to the dementia syndrome and should improve clinical detection and enrollment for clinical trials.
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stress and burden among caregivers of patients with Lewy Body dementia
Gerontologist, 2011Co-Authors: Amanda Leggett, Steven H Zarit, Angela Taylor, James E GalvinAbstract:Purpose: Patients with Lewy Body dementia (LBD) may present a unique set of symptoms and challenges to family caregivers compared with other types of dementia. Prominent difficulties include motor impair ment, activities of daily living (ADLs) disability, recurrent behavioral and emotional problems (BEPs), and diagnostic difficulties. These problems are likely to affect caregivers’ subjective burden. Design and Methods: The present study used data from an Internet survey conducted by the Lewy Body Dementia Association. Respondents were 611 people who indicated that they were currently involved in the care of their relative with LBD. Subjective burden was assessed with a 12-item short version of the Zarit Burden Interview. Results: A factor analysis revealed 3 dimensions of burden: role strain, personal strain, and worry about performance. Multiple regressions were used to examine predictors of these dimensions. BEPs, ADL disability, isolation, caregiver age, and patient gender were significant predictors of specific factors. Falls, formal service use, difficulty finding a physician, and evaluation of the physician had no significant associations with burden. Implications: These findings highlight burden experiences by caregivers of patients with LBD and the impact of BEPs, ADL assistance, and awareness about LBD on subjective burden.
John T Obrien - One of the best experts on this subject based on the ideXlab platform.
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improving the diagnosis and management of Lewy Body dementia the diamond Lewy research programme including pilot cluster rct
Programme Grants for Applied Research, 2021Co-Authors: Alan J Thomas, John T Obrien, Johnpaul Taylor, Claire Bamford, Luke Vale, Sarah Hill, Louise Allan, Tracy Finch, Richard J Q McnallyAbstract:Background Lewy Body dementia, comprising both dementia with Lewy bodies and Parkinson’s disease dementia, is the second commonest cause of neurodegenerative dementia. Existing evidence suggests that it is underdiagnosed and without a consistent approach to management. Objectives To improve the diagnosis and management of Lewy Body dementia by (1) understanding current diagnostic practice for dementia with Lewy bodies and Parkinson’s disease dementia; (2) identifying barriers to and facilitators of diagnosis and management; (3) developing evidence-based assessment toolkits to improve diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia; (4) producing a management toolkit to facilitate management; and (5) undertaking a pilot cluster randomised clinical trial. Design Work package 1 assessed clinical diagnostic rates from case notes for dementia with Lewy bodies and Parkinson’s disease dementia before and after (work package 1 repeated) introduction of an assessment toolkit. In work package 2, we developed a management toolkit for Lewy Body dementia. In work package 3, we developed assessment toolkits for dementia with Lewy bodies and Parkinson’s disease dementia and piloted these and the management toolkit in a clinical service. In work package 4, we undertook a pilot study of 23 services in nine NHS trusts that were cluster randomised to receiving and using the management toolkit or standard care. Work package 5 comprised a series of qualitative studies, examining barriers to and facilitators of diagnosis and management. Setting Secondary care memory assessment and movement disorder services in England. Interventions Assessment toolkits for Lewy Body dementia consisted of questions for diagnostic symptoms, and management toolkits comprised 161 guidance statements grouped under five symptom domains. Review methods The systematic reviews of pharmacological and non-pharmacological management were based on published literature, with meta-analysis when possible, following a search of several electronic databases and the grey literature using terms related to Lewy Body dementia, without restriction on time or language. Participants Participants aged ≥ 50 years diagnosed with dementia with Lewy bodies or Parkinson’s disease dementia and, for work package 1 and work package 1 repeated, non-dementia with Lewy bodies and non-Parkinson’s disease dementia controls. The qualitative studies included people with Lewy Body dementia, carers and professionals. Main outcome measures For work packages 1 and 1 repeated, diagnostic rates for dementia with Lewy bodies and Parkinson’s disease dementia as a proportion of all dementia or Parkinson’s disease. For work packages 2 and 3, the production of diagnostic and management toolkits. For work package 4, feasibility of undertaking a cluster randomised trial of the toolkits, measured by number of participants recruited and use of the toolkits, assessed qualitatively. Results Work package 1 – 4.6% of dementia cases in secondary care received a dementia with Lewy bodies diagnosis (with significant differences in diagnostic rates between services) and 9.7% of those with Parkinson’s disease had a diagnosis of Parkinson’s disease dementia. There was evidence of delays in diagnosis for both dementia with Lewy bodies and Parkinson’s disease dementia compared with control patients, and the costs of dementia with Lewy bodies and Parkinson’s disease dementia were also greater than those for matched controls (p 80% were retained in the study at 6 months. Work package 5 – barriers to diagnosis and management of Lewy Body dementia were complex. Managing Lewy Body dementia often requires input from a range of specialties and, therefore, care pathways may be fragmented. Positive attitudes to diagnosing Lewy Body dementia, working with a team with expertise in Lewy Body dementia and opportunities for cross-specialty discussion of patients with complex needs facilitated diagnosis and management. The toolkits were generally well received, particularly the management toolkit. Implementation, however, varied, reflecting differences in attitudes, skills, time and local leadership. Work package 1 repeated – following introduction of the assessment toolkit, we found that 9.7% of dementia cases had dementia with Lewy bodies (a significant increase from baseline; p = 0.0019), but Parkinson’s disease dementia rates were similar (8.2%) to baseline. Limitations We included only two geographical regions and evidence informing the management toolkit was limited. Work package 4 was a pilot study and, therefore, we did not set out to assess the extent to which use of the management toolkit altered outcomes at the individual patient level. We noted implementation of the toolkits was variable. The increase in diagnostic rates in dementia with Lewy bodies following introduction of the assessment toolkits cannot be necessarily causally attributed to them. Conclusions Dementia with Lewy bodies and Parkinson’s disease dementia were diagnosed in secondary care NHS services, with a lower frequency (around half) than that expected from known prevalence rates. The introduction of assessment toolkits for dementia with Lewy bodies and Parkinson’s disease dementia was associated with increased diagnostic rates of dementia with Lewy bodies, but not Parkinson’s disease dementia. Qualitative studies indicated inherent complexities of the disease itself, with treatment requiring input from different specialties and the potential for fragmented services, a workforce with variable training and confidence in Lewy Body dementia, and negative attitudes towards diagnosis. The cluster randomised pilot trial demonstrated that patients could be successfully recruited, and provided preliminary evidence that the toolkits could be implemented in clinical services. Future work The evidence base informing the management of Lewy Body dementia is limited, especially for non-pharmacological interventions. More well-designed randomised controlled trials for both cognitive and non-cognitive symptoms are needed. Trial registration Current Controlled Trials ISRCTN11083027. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 7. See the NIHR Journals Library website for further project information.
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new evidence on the management of Lewy Body dementia
Lancet Neurology, 2020Co-Authors: Johnpaul Taylor, Daniel Weintraub, Ian G Mckeith, David J Burn, Alan J Thomas, Brad F Boeve, Claire Bamford, Louise M Allan, John T ObrienAbstract:Summary Dementia with Lewy bodies and Parkinson's disease dementia, jointly known as Lewy Body dementia, are common neurodegenerative conditions. Patients with Lewy Body dementia present with a wide range of cognitive, neuropsychiatric, sleep, motor, and autonomic symptoms. Presentation varies between patients and can vary over time within an individual. Treatments can address one symptom but worsen another, which makes disease management difficult. Symptoms are often managed in isolation and by different specialists, which makes high-quality care difficult to accomplish. Clinical trials and meta-analyses now provide an evidence base for the treatment of cognitive, neuropsychiatric, and motor symptoms in patients with Lewy Body dementia. Furthermore, consensus opinion from experts supports the application of treatments for related conditions, such as Parkinson's disease, for the management of common symptoms (eg, autonomic dysfunction) in patients with Lewy Body dementia. However, evidence gaps remain and future clinical trials need to focus on the treatment of symptoms specific to patients with Lewy Body dementia.
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neural correlates of attention executive dysfunction in Lewy Body dementia and alzheimer s disease
Human Brain Mapping, 2016Co-Authors: Michael J Firbank, Xenia Kobeleva, George Cherry, Alison Killen, Peter Gallagher, David J Burn, Alan J Thomas, John T Obrien, Johnpaul TaylorAbstract:Attentional and executive dysfunction contribute to cognitive impairment in both Lewy Body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy Body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto-parieto-occipital network activation in all groups, Alzheimer's disease and Lewy Body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy Body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention-executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases. Hum Brain Mapp 37:1254–1270, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Koichi Wakabayashi - One of the best experts on this subject based on the ideXlab platform.
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alteration of autophagosomal proteins lc3 gabarap and gate 16 in Lewy Body disease
Neurobiology of Disease, 2011Co-Authors: Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi WakabayashiAbstract:Macroautophagy is a dynamic process whereby cytoplasmic molecules are sequestered within autophagosomes. Based on amino acid similarity, there exist two groups of mammalian autophagy-related gene (Atg) 8 homologues [microtubule-associated protein 1 light chain 3 (LC3) and γ-aminobutyric-acid type A receptor associated proteins (GABARAPs)], which play essential role in autophagosomal formation. Despite recent progress in studies on LC3, the other Atg8 homologues remain to be poorly understood, especially in pathological condition. In this study, we determined whether Atg8 homologues are affected in Lewy Body disease, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Our findings indicated that biochemical and pathological properties of LC3 were altered and that the level of LC3 was increased in an insoluble fraction from the brain of patients with DLB, whereas the level of GABARAPs was decreased in DLB. Furthermore, immunohistochemical staining revealed that both LC3 and GABARAPs were localized in Lewy bodies in PD and DLB. These findings suggest that autophagic function is impaired through alteration of Atg8 homologues in Lewy Body disease.
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Proteinase K-resistant alpha-synuclein is deposited in presynapses in human Lewy Body disease and A53T alpha-synuclein transgenic mice.
Acta neuropathologica, 2010Co-Authors: Kunikazu Tanji, Fumiaki Mori, Junsei Mimura, Ken Itoh, Akiyoshi Kakita, Hitoshi Takahashi, Koichi WakabayashiAbstract:Abnormally modified alpha-synuclein is a pathological hallmark of Parkinson's disease and the other alpha-synucleinopathies. Since proteinase K (PK) treatment is known to enhance the immunoreactivity of abnormal alpha-synuclein, we immunohistochemically examined the brain of transgenic (Tg) mice expressing human mutant A53T alpha-synuclein using this retrieval method. PK treatment abolished the immunoreactivity of alpha-synuclein in abnormal inclusions as well as of endogenous alpha-synuclein in Tg mice, whereas PK-resistant alpha-synuclein was found in the presynaptic nerve terminals, especially in the hippocampus and temporal cortex. In human Lewy Body disease, PK-resistant alpha-synuclein was deposited in Lewy bodies and Lewy neurites, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Biochemical analysis revealed that PK-resistant alpha-synuclein was detected in the presynaptic fraction in Tg mice and human Lewy Body disease. Although PK-resistant alpha-synuclein was found in the presynapse in Tg mice even at 1 week of age, it was not phosphorylated until at least 8 months of age. Moreover, PK-resistant alpha-synuclein in the presynapse was not phosphorylated in human Lewy Body disease. These findings suggest that phosphorylation is not necessary to cause the conversion of soluble form to PK-resistant alpha-synuclein. Considering that native alpha-synuclein is a soluble protein localized to the presynaptic terminals, our findings suggest that PK-resistant alpha-synuclein may disturb the neurotransmission in alpha-synucleinopathies.
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cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy Body disease
Acta Neuropathologica, 2005Co-Authors: Satoshi Orimo, Fumiaki Mori, Koichi Wakabayashi, Takeshi Amino, Yoshinori Itoh, Atsushi Takahashi, Tohru Kojo, Toshiki Uchihara, Kuniaki Tsuchiya, Hitoshi TakahashiAbstract:Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I]MIBG myocardial scintigraphy has been reported in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We hypothesized that cardiac sympathetic denervation might account for the pathomechanism. To elucidate the extent, frequency and pattern of cardiac sympathetic nerve involvement in Lewy Body disease and related neurodegenerative disorders, we immunohistochemically examined heart tissues from patients with PD (n=11), DLB (n=7), DLB with Alzheimer’s disease (DLB/AD; n=4), multiple system atrophy (MSA; n=8), progressive supranuclear palsy (PSP; n=5), pure AD (n=10) and control subjects (n=5) together with sympathetic ganglia from patients with PD (n=5) and control subjects (n=4), using an antiBody against tyrosine hydroxylase (TH). TH-immunoreactive nerve fibers in the hearts had almost entirely disappeared in nearly all the patients with PD, DLB and DLB/AD, whereas they were well preserved in all the patients with PSP and pure AD as well as in all except for one patient with MSA. In PD, neurons in the sympathetic ganglia were preserved in all except for one patient. Decreased cardiac uptake of MIBG in Lewy Body disease reflects actual cardiac sympathetic denervation, which precedes the neuronal loss in the sympathetic ganglia.
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Lewy Body type degeneration in cardiac plexus in parkinson s and incidental Lewy Body diseases
Neurology, 1999Co-Authors: K Iwanaga, Koichi Wakabayashi, M Yoshimoto, Itsuro Tomita, Hideyo Satoh, H Takashima, Akira Satoh, Makiko Seto, Mitsuhiro Tsujihata, Hitoshi TakahashiAbstract:Article abstract Heart tissues of patients with PD or incidental Lewy Body (LB) disease (ILBD) were examined by light and electron microscopy. LBs and α-synuclein–positive neurites were identified in the hearts from 9 of 11 patients with PD and from 7 of 7 patients with ILBD. LBs were present in both tyrosine hydroxylase-positive and -negative nerve processes, which are nerves of extrinsic sympathetic and intrinsic origin, respectively. These findings provide histologic evidence that the postganglionic sympathetic and intrinsic neurons in the heart are involved in the PD disease process.
Ellen A A Nollen - One of the best experts on this subject based on the ideXlab platform.
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observation of an α synuclein liquid droplet state and its maturation into Lewy Body like assemblies
Journal of Molecular Cell Biology, 2021Co-Authors: Maarten C Hardenberg, Tessa Sinnige, Sam Casford, Samuel T Dada, Chetan Poudel, Elizabeth A Robinson, Monika Fuxreiter, Clemens Kaminksi, Gabriele Kaminski S Schierle, Ellen A A NollenAbstract:Misfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson's disease (PD). A large Body of evidence shows that α-synuclein can aggregate into amyloid fibrils, but the relationship between α-synuclein self-assembly and Lewy Body formation remains unclear. Here, we show, both in vitro and in a Caenorhabditis elegans model of PD, that α-synuclein undergoes liquid‒liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-Body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.
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Observation of an α-synuclein liquid droplet state and its maturation into Lewy Body-like assemblies.
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Hardenberg, Maarten C, Sinnige Tessa, Casford Sam, Poudel Chetan, Robinson, Elizabeth A, Fuxreiter Monika, Kaminski Gabriele, Dada, Samuel T, Kaminksi, Clemens F, Ellen A A NollenAbstract:Misfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson's disease (PD). A large Body of evidence shows that α-synuclein can aggregate into amyloid fibrils, but the relationship between α-synuclein self-assembly and Lewy Body formation remains unclear. Here, we show, both in vitro and in a Caenorhabditis elegans model of PD, that α-synuclein undergoes liquid‒liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-Body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.Wellcome Trust (065807/Z/01/Z) (203249/Z/16/Z). Also, the UK Medical Research Council (MRC) (MR/K02292X/1), Alzheimer Research UK (ARUK) (ARUK-PG013-14), Michael J Fox Foundation (16238) and from Infinitus China Ltd
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Observation of an α-1synuclein liquid droplet state and its maturation into Lewy Body-like assemblies
Journal of Molecular Cell Biology, 2020Co-Authors: Hardenberg, Maarten C, Sinnige Tessa, Casford Sam, Dada Samuel, Poudel Chetan, Robinson, Elizabeth A, Fuxreiter Monika, Kaminski Clemens, Kaminski Gabriele, Ellen A A NollenAbstract:Misfolded a-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson’s disease. A large Body of evidence shows that a-synuclein can aggregate into amyloid fibrils, but the relationship between a-synuclein self-assembly and Lewy Body formation remains unclear. Here we show, both in vitro and in a C. elegans model of Parkinson’s disease, that a-synuclein undergoes liquid-liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-Body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of a-synuclein condensates in the presence of lipids and other cellular components.Wellcome Trust (065807/Z/01/Z) (203249/Z/16/Z). Also, the UK Medical Research Council (MRC) (MR/K02292X/1), Alzheimer Research UK (ARUK) (ARUK-PG013-14), Michael J Fox Foundation (16238) and from Infinitus China Ltd
