Laboratoire Of Neuropathologie Raymond Escourolle
Laboratoire Of Neuropathologie Raymond Escourolle
Duyckaerts C.,Laboratoire Of Neuropathologie Raymond Escourolle
Revue Neurologique | Year: 2013
Accumulation of specific proteins has replaced loss of specific populations of neurons in the definition of most neurodegenerative diseases. In some cases, the amino-acid sequence of the protein that accumulates is altered by a mutation in the gene that codes for it but most generally, the primary structure is normal. Much evidence from human neuropathology has been collected over the years indicating that the progression of the lesions in such neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy follow the neuroanatomical connections. More recently, injection of aggregates of the specific proteins in the brain of experimental animals has been attempted in various experimental settings. Brain homogenates containing Aβ aggregates induce the early development of Aβ deposits in APP transgenic mice. Brain homogenates from various human tauopathies induce tau aggregates in transgenic mice expressing normal human tau. Finally, synthetic preformed fibrils of alpha-synuclein initiate the development of alpha-synuclein accumulation resembling Parkinson's disease in wild-type mice. Experiments in cell cultures suggest that the protein has to be in some specific state of oligomerization or fibrillation to be endocytosed and transported by the neuron. These data suggest that the protein that accumulates in a specific disease is initially misfolded and that this misfolding contaminates normal protein in a prion-like manner - in some cases through the neuronal connections. © 2013 Elsevier Masson SAS.
Pham C.-T.,Laboratoire Of Neuropathologie Raymond Escourolle |
de Silva R.,University College London |
Haik S.,Laboratoire Of Neuropathologie Raymond Escourolle |
Verny M.,University Pierre and Marie Curie |
And 6 more authors.
Neurobiology of Aging | Year: 2011
The influence of age on the prevalence of argyrophilic grain disease has been analyzed in the hippocampus from 29 centenarians. Argyrophilic grains were detected in 12 cases with Gallyas silver method, in 24 cases with anti-exon 10 (RD4) immunohistochemistry, in all the cases with a phospho-independent anti-tau (piTau) antibody and with a monoclonal antibody against Ser202 of the tau protein (AT8), suggesting a maturation of the grains. Ballooned neurons were found in the hippocampus of 12 cases in which grains were, on average, more abundant. Coiled bodies were found in 26, 15 and 13 cases respectively with piTau antibody, RD4 and Gallyas method. Cases with coiled bodies had a higher density of grains. The mean density of grains did not differ in the patients with or without dementia. The prevalence of tau-positive grains has been underestimated in the very old population. As neurofibrillary tangles, they appear to be a constant accompaniment of age but, contrarily to neurofibrillary tangles, do not seem to be strongly associated with dementia. © 2009 Elsevier Inc.
Chapuis J.,University of Lille Nord de France |
Hansmannel F.,University of Lille Nord de France |
Mounier A.,University of Lille Nord de France |
Van Cauwenberghe C.,Neurodegenerative Brain Diseases Group |
And 48 more authors.
Molecular Psychiatry | Year: 2013
Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele ∼28 kb upstream of BIN1, which increased (i) transcriptional activity in vitro, (ii) BIN1 expression levels in human brain and (iii) AD risk in three independent case-control cohorts (Meta-analysed Odds ratio of 1.20 (1.14-1.26) (P=3.8 × 10 -11)). Interestingly, decreased expression of the Drosophila BIN1 ortholog Amph suppressed Tau-mediated neurotoxicity in three different assays. Accordingly, Tau and BIN1 colocalized and interacted in human neuroblastoma cells and in mouse brain. Finally, the 3 bp insertion was associated with Tau but not Amyloid loads in AD brains. We propose that BIN1 mediates AD risk by modulating Tau pathology. © 2013 Macmillan Publishers Limited.
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.
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.