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Le Touquet – Paris-Plage, France

Eisele Y.S.,Scripps Research Institute | Duyckaerts C.,Laboratoire Of Neuropathologie Raymond Escourolle
Acta Neuropathologica | Year: 2016

In brains of patients with Alzheimer’s disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way—although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term “propagons”. Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology. © 2015, Springer-Verlag Berlin Heidelberg. Source


Petiet A.,French National Center for Scientific Research | Delatour B.,Laboratoire Of Neuropathologie Raymond Escourolle | Dhenain M.,CEA Fontenay-aux-roses
Methods in Molecular Biology | Year: 2011

Alzheimer's disease (AD) is an important social and economic issue for our societies. The development of therapeutics against this severe dementia requires assessing the effects of new drugs in animal models thanks to dedicated biomarkers. According to the amyloid cascade hypothesis, β-amyloid deposits are at the origin of most of the lesions associated with AD. These extracellular deposits are therefore one of the main targets in therapeutical strategies. Aβ peptides can be revealed histologically with specific dyes or antibodies, or by magnetic resonance microscopy (μMRI) that uses their association with iron as a source of signal. The microscopic size of the lesions necessitates the development of specific imaging protocols. Most protocols use T 2-weighted sequences that reveal the aggregates as hypointense spots. This chapter describes histological methods that reveal amyloid plaques with specific stains and MR-imaging protocols for in vivo and ex vivo MR imaging of AD mice. © 2011 Springer Science+Business Media, LLC. Source


Hauw J.-J.,University Pierre and Marie Curie | Hauw J.-J.,Institute of Veille Sanitaire | Hauw J.-J.,Laboratoire Of Neuropathologie Raymond Escourolle | Hausser-Hauw C.,EEG EMG Unit | And 4 more authors.
Journal of Neuropathology and Experimental Neurology | Year: 2011

Sleep disorders are important manifestations of neurodegenerativediseases and sometimes are clinically evident well before the onset of other neurological manifestations. This review addresses theneuroanatomical basis and the mechanisms of sleep regulation in humans in relation to the neuropathology of entities associated with sleep disturbances in selected diseases, including Alzheimer disease, progressive supranuclear palsy, Lewy body disorders, multiple-system atrophy, and fatal familial insomnia. This includes abnormalities of circadian rhythm, insomnia, narcolepsy, rapid eye movements sleep behavior disorders, and excessive daytime sleepiness. © 2011 by the American Association of Neuropathologists, Inc. Source


Bouafia A.,French Institute of Health and Medical Research | Golmard J.-L.,University Pierre and Marie Curie | Thuries V.,Laboratoire Of Neuropathologie Raymond Escourolle | Sazdovitch V.,French Institute of Health and Medical Research | And 6 more authors.
Neuropathology and Applied Neurobiology | Year: 2014

Aims: Although demyelination is an important cause of neurological deficits in multiple sclerosis (MS), recently axonal pathology and concomitant involvement of sodium channels (Nav) became a focus of major interest. Studies in experimental autoimmune encephalomyelitis (EAE) and MS have shown diffuse expression of Nav1.6 and Nav1.2 along demyelinated axons. However, the relation between this expression by the axon and its environment is not yet known. The aim of this exploratory study was to identify the neuropathological characteristics of the plaque associated with the changes of sodium channel axonal expression. Methods: We analysed by immunohistochemistry the expression of Nav1.6 and Nav1.2 along demyelinated axons in 64 plaques from 12 MS cases. To characterize the plaques, we used Luxol fast blue staining and immunohistochemistry for myelin basic protein, microglia/macrophages, T and B cells, reactive astrocytes and axonal lesions performed on sections of formalin-fixed, paraffin-embedded tissue. Results: The presence of diffuse axonal expression of Nav1.6 was equally distributed between active demyelinating and inactive not demyelinating plaques based on presence or absence of myelin laden macrophages respectively. However, presence of diffuse axonal expression of Nav1.6 was more frequent within plaques with T cells infiltrate and microglial hyperplasia. On the other hand, Nav1.2 diffuse axonal expression seemed to be independent of the neuropathological environment of the plaque. Conclusions: The cellular environment of the axon influences the differential expression of Nav channels. A better understanding of the influence of the inflammation on sodium channels mediated axonal degeneration could offer therapeutic perspectives. © 2013 British Neuropathological Society. Source


Soubrier M.,Service de Rhumatologie | Haik S.,French Institute of Health and Medical Research | Haik S.,Laboratoire Of Neuropathologie Raymond Escourolle | Hauw J.-J.,Laboratoire Of Neuropathologie Raymond Escourolle | And 3 more authors.
Joint Bone Spine | Year: 2010

We describe a patient in whom sporadic Creutzfeldt-Jakob disease (sCJD) occured one year after the onset of etanercept therapy for rheumatoid arthritis (RA). This association could be a chance occurrence. However, TNF-α has been implicated in the pathogenesis of neurodegeneration in sCJD and etanercept might worsen the disease. Such an aggravation has been observed in multiple sclerosis, in which TNF-α is the key mediator of demyelination. It may be of interest studying the impact of treatment with TNF-α antagonists on prevalence and incidence of those neurodegenerative diseases involving TNF-α mediation, such as Alzheimer disease. © 2009 Société française de rhumatologie. Source

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