ALPHA SYNUCLEIN IMMUNOREACTIVITY IN DEMENTIA WITH LEWY BODIES

1999 ◽  
Vol 58 (5) ◽  
pp. 553
Author(s):  
E Gómez-Tortosa ◽  
K L Newell ◽  
M C Irizarry ◽  
M Albert ◽  
J H Growdon ◽  
...  
2017 ◽  
Vol 13 (7S_Part_7) ◽  
pp. P338-P338 ◽  
Author(s):  
Inger van Steenoven ◽  
Nour K. Majbour ◽  
Nishant N. Vaikath ◽  
Henk W. Berendse ◽  
Wiesje M. van der Flier ◽  
...  

Medicina ◽  
2012 ◽  
Vol 48 (1) ◽  
pp. 1 ◽  
Author(s):  
Jūratė Macijauskienė ◽  
Vita Lesauskaitė

Dementia with Lewy bodies was first recognized as a separate entity about 30 years ago. The prevalence varies from 0% to 5% in the general population, and this disease accounts for 0% to 30.5% of all dementia cases. Dementia with Lewy bodies is considered the second most common cause of degenerative dementia after Alzheimer’s disease. The disease is characterized by alpha-synuclein immunoreactive protein deposits in both neurons and glial cells. The protein deposits are especially prominent in dopaminergic neurons, where they can be detected using conventional histological stains, such as hematoxylin and eosin, and are commonly referred to as Lewy bodies. The diagnosis of dementia with Lewy bodies is based on the presence of dementia as well as 2 of the following 3 core diagnostic features: 1) fluctuating cognition, 2) visual hallucinations, and 3) movement disorder. Diagnostic tests include laboratory data, structural and functional imaging, and electroencephalography. Differential diagnosis of dementia with Lewy bodies focuses on other later life dementia syndromes, other parkinsonian diseases (Parkinson’s disease, progressive supranuclear palsy, corticobasal degeneration), and primary psychiatric illnesses. There is type 1b evidence to support treatment with cholinesterase inhibitors. Glutamatergic and dopaminergic therapies are used as well. Standard neuroleptics are contraindicated, and atypical agents should be used cautiously. Nonpharmacologic measures – therapeutic environment, psychological and social support, physical activity, behavioral management strategies, caregivers’ education and support, and different services – could be suggested.


2019 ◽  
Vol 78 (10) ◽  
pp. 877-890 ◽  
Author(s):  
Norihito Uemura ◽  
Maiko T Uemura ◽  
Angela Lo ◽  
Fares Bassil ◽  
Bin Zhang ◽  
...  

Abstract Synucleinopathies are composed of Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Alpha-synuclein (α-Syn) forms aggregates mainly in neurons in PD and DLB, while oligodendroglial α-Syn aggregates are characteristic of MSA. Recent studies have demonstrated that injections of synthetic α-Syn preformed fibrils (PFFs) into the brains of wild-type (WT) animals induce intraneuronal α-Syn aggregates and the subsequent interneuronal transmission of α-Syn aggregates. However, injections of α-Syn PFFs or even brain lysates of patients with MSA have not been reported to induce oligodendroglial α-Syn aggregates, raising questions about the pathogenesis of oligodendroglial α-Syn aggregates in MSA. Here, we report that WT mice injected with mouse α-Syn (m-α-Syn) PFFs develop neuronal α-Syn pathology after short postinjection (PI) intervals on the scale of weeks, while oligodendroglial α-Syn pathology emerges after longer PI intervals of several months. Abundant oligodendroglial α-Syn pathology in white matter at later time points is reminiscent of MSA. Furthermore, comparison between young and aged mice injected with m-α-Syn PFFs revealed that PI intervals rather than aging correlate with oligodendroglial α-Syn aggregation. These results provide novel insights into the pathological mechanisms of oligodendroglial α-Syn aggregation in MSA.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Mirko Bibl ◽  
Hermann Esselmann ◽  
Piotr Lewczuk ◽  
Claudia Trenkwalder ◽  
Markus Otto ◽  
...  

We studied the diagnostic value of CSF Aβ42/tau versus low Aβ1–42% and high Aβ1–40ox% levels for differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), respectively. CSF of 45 patients with AD, 15 with DLB, 21 with Parkinson's disease dementia (PDD), and 40 nondemented disease controls (NDC) was analyzed by Aβ-SDS-PAGE/immunoblot and ELISAs (Aβ42 and tau). Aβ42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers were Aβ1–42% and Aβ1–40ox% for AD and DLB, respectively. AD and DLB could be differentiated by both Aβ1–42% and Aβ1–40ox% with an accuracy of 80% at minimum. Thus, we consider Aβ1–42% and Aβ1–40ox% to be useful biomarkers for AD and DLB, respectively. We propose further studies on the integration of Aβ1–42% and Aβ1–40ox% into conventional assay formats. Moreover, future studies should investigate the combination of Aβ1–40ox% and CSF alpha-synuclein for the diagnosis of DLB.


Author(s):  
Carlos Henrique Ferreira Camargo ◽  
Marcus Vinicius Della-Coletta ◽  
Delson José da Silva ◽  
Hélio A. G. Teive

Alpha-synuclein is a protein that forms a major component of abnormal neuronal aggregates known as Lewy bodies. A particular group of neurodegenerative disorders (NDs) is characterized by the abnormal accumulation of α-synuclein; termed the α-synucleinopathies, this group includes Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Lysosomal storage diseases have also been linked to α-synuclein toxicity. Several therapeutic targets have been chosen among steps of metabolism of α-synuclein. Reducing α-synuclein synthesis or expression and increasing the clearance can be achieved in many ways. The development of immunotherapeutic approaches targeting α-synuclein has received considerable attention in recent years. The aim of this chapter is to present the α-synucleinopathies, as well as to present the most recent researches about treatment of synucleinopathies based on knowledge of the pathophysiology of α-synuclein pathways.


2020 ◽  
Vol 17 (3) ◽  
pp. 1061-1074 ◽  
Author(s):  
Julia Marschallinger ◽  
Barbara Altendorfer ◽  
Edward Rockenstein ◽  
Miriam Holztrattner ◽  
Julia Garnweidner-Raith ◽  
...  

Abstract Dementia with Lewy bodies (DLB) represents a huge medical need as it accounts for up to 30% of all dementia cases, and there is no cure available. The underyling spectrum of pathology is complex and creates a challenge for targeted molecular therapies. We here tested the hypothesis that leukotrienes are involved in the pathology of DLB and that blocking leukotrienes through Montelukast, a leukotriene receptor antagonist and approved anti-asthmatic drug, might alleviate pathology and restore cognitive functions. Expression of 5-lipoxygenase, the rate-limiting enzyme for leukotriene production, was indeed elevated in brains with DLB. Treatment of cognitively deficient human alpha-synuclein overexpressing transgenic mice with Montelukast restored memory. Montelukast treatment resulted in modulation of beclin-1 expression, a marker for autophagy, and in a reduction in the human alpha-synulcein load in the transgenic mice. Reducing the protein aggregation load in neurodegenerative diseases might be a novel model of action of Montelukast. Moreover, this work presents leukotriene signaling as a potential drug target for DLB and shows that Montelukast might be a promising drug candidate for future DLB therapy development.


Sign in / Sign up

Export Citation Format

Share Document