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Genome-wide association studies (GWAS) have identified PICALM as one of the most significant susceptibility loci for late-onset Alzheimer's disease (AD) after APOE and BIN1. PICALM is a clathrin-adaptor protein and plays critical roles in clathrin-mediated endocytosis and in autophagy. PICALM modulates brain amyloid ß (Aß) pathology and tau accumulation. We have previously reported that soluble PICALM protein level is reduced in correlation with abnormalities of autophagy markers in the affected brain areas of neurodegenerative diseases including AD, sporadic tauopathies and familial cases of frontotemporal lobar degeneration with tau-immunoreactive inclusions (FTLD-tau) with mutations in the microtubule-associated protein tau (MAPT) gene. It remains unclarified whether in vivo PICALM reduction could either trigger or influence tau pathology progression in the brain. In this study, we confirmed a significant reduction of soluble PICALM protein and autophagy deficits in the post-mortem human brains of FTLD-tau-MAPT (P301L, S364S and L266V). We generated a novel transgenic mouse line named Tg30xPicalm+/- by crossing Tg30 tau transgenic mice with Picalm-haploinsufficient mice to test whether Picalm reduction may modulate tau pathology. While Picalm haploinsufficiency did not lead to any motor phenotype or detectable tau pathology in mouse brains, Tg30xPicalm+/- mice developed markedly more severe motor deficits than Tg30 by the age of 9 months. Tg30xPicalm+/- had significantly higher pathological tau levels in the brain, an increased density of neurofibrillary tangles compared to Tg30 mice and increased abnormalities of autophagy markers. Our results demonstrate that Picalm haploinsufficiency in transgenic Tg30 mice significantly aggravated tau pathologies and tau-mediated neurodegeneration, supporting a role for changes in Picalm expression as a risk/sensitizing factor for development of tau pathology and as a mechanism underlying the AD risk associated to PICALM., info:eu-repo/semantics/published

Studies supporting a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline have heightened the allure of tau and tau-related mechanisms as therapeutic targets. In February 2020, leading tau experts from around the world convened for the first-ever Tau2020 Global Conference in Washington, DC, co-organized and cosponsored by the Rainwater Charitable Foundation, the Alzheimer's Association, and CurePSP. Representing academia, industry, government, and the philanthropic sector, presenters and attendees discussed recent advances and current directions in tau research. The meeting provided a unique opportunity to move tau research forward by fostering global partnerships among academia, industry, and other stakeholders and by providing support for new drug discovery programs, groundbreaking research, and emerging tau researchers. The meeting also provided an opportunity for experts to present critical research-advancing tools and insights that are now rapidly accelerating the pace of tau research., info:eu-repo/semantics/published

Among genetic susceptibility loci associated with late-onset Alzheimer disease (LOAD), genetic polymorphisms identified in genes encoding lipid carriers led to the hypothesis that a disruption of lipid metabolism could promote disease progression. We previously reported that amyloid precursor protein (APP) involved in Alzheimer disease (AD) physiopathology impairs lipid synthesis needed for cortical networks' activity and that activation of peroxisome proliferator-activated receptor α (PPARα), a metabolic regulator involved in lipid metabolism, improves synaptic plasticity in an AD mouse model. These observations led us to investigate a possible correlation between PPARα function and full-length APP expression. Here, we report that PPARα expression and activation were inversely related to APP expression both in LOAD brains and in early-onset AD cases with a duplication of the APP gene, but not in control human brains. Moreover, human APP expression decreased PPARA expression and its related target genes in transgenic mice and in cultured cortical cells, while opposite results were observed in APP-silenced cortical networks. In cultured neurons, APP-mediated decrease or increase in synaptic activity was corrected by a PPARα-specific agonist and antagonist, respectively. APP-mediated control of synaptic activity was abolished following PPARα deficiency, indicating a key function of PPARα in this process., SCOPUS: ar.j, info:eu-repo/semantics/published

Human tauopathies are neurodegenerative diseases with accumulation of abnormally phosphorylated and aggregated tau proteins forming neurofibrillary tangles (NFT). We investigated the development of tau pathology in aged cat brains as a model of NFT formation occurring spontaneously during aging.In 4 out of 6 cats aged between 18 and 21 years, we found a somatodendritic accumulation of phosphorylated and aggregated tau in neurons and oligodendrocytes. Two of these 4 cats had no amyloid immunoreactivity. These tau inclusions were mainly composed of 4R tau isoforms, of straight filaments and colocalized with the active form of the glycogen synthase kinase-3 (GSK3). Cat brains with a tau pathology showed a significant cortical atrophy and neuronal loss.We demonstrate in this study the presence of a tau pathology in aged cat brains that develops independently of amyloid deposits. The colocalization of the active form of the GSK3 with tau inclusions as observed in human tauopathies suggests that this kinase could be responsible for the abnormal tau phosphorylation observed in aged cat brains, representing a mechanism of tau pathology development shared between a naturally occurring tauopathy in aged cats and human tauopathies., SCOPUS: ar.j, info:eu-repo/semantics/published

A murine osmotic demyelination syndrome (ODS) model of the central nervous system included the relay thalamic ventral posterolateral (VPL) and ventral posteromedial (VPM) nuclei. Morphologic comparisons between treatments have revealed oligodendrocyte changes and, already 12 hours following the osmolality restoration, some heavily contrasted oligodendrocytes formed a unique intracellular primary cilium. This unique structure, found in vivo, in mature CNS oligodendrocytes, could account for a local awakening of some of the developmental proteome as it can be expressed in oligodendrocyte precursor cells. This resilience accompanied the emergence of arl13b protein expression along with restoration of nerve cell body axon hillocks shown in a previous issue of this journal. Additionally, the return of several thalamic oligodendrocyte fine features (nucleus, organelles) was shown 36 h later, including some mitosis. Those cell restorations and recognized translational activities comforted that local repairs could again take place, due to oligodendrocyte resilience after ODS instead or added to a postulated immigration of oligodendrocyte precursor cells distant from the sites of myelinolysis., info:eu-repo/semantics/published

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Adult hippocampal neurogenesis (AHN) has been widely confirmed in mammalian brains. A growing body of evidence points to the fact that AHN sustains hippocampal-dependent functions such as learning and memory. Impaired AHN has been reported in post-mortem human brain hippocampus of Alzheimer's disease (AD) and is considered to contribute to defects in learning and memory. Neurofibrillary tangles (NFTs) and amyloid plaques are the two key neuropathological hallmarks of AD. NFTs are composed of abnormal tau proteins accumulating in many brain areas during the progression of the disease, including in the hippocampus. The physiological role of tau and impact of tau pathology on AHN is still poorly understood. Modifications in AHN have also been reported in some tau transgenic and tau-deleted mouse models. We present here a brief review of advances in the relationship between development of tau pathology and AHN in AD and what insights have been gained from studies in tau mouse models., info:eu-repo/semantics/published

International audience; Alzheimer’s disease (AD) is the most common form of dementia. Its prevalence will significantlyincrease in the coming decades, whereas no efficient treatment is currently available. AD hastwo main neuropathological lesions: amyloid plaques and neurofibrillary tangles (NFTs). Amyloidplaques are composed of amyloid ß (Aß) peptides cleaved from the Amyloid Precursor Protein(APP) (Glenner and Wong, 1984). NFTs, present in the brain of AD and related neurodegenerativediseases, are constituted of tau proteins (Brion et al., 1985) in hyperphosphorylated and aggregatedform (Wang and Mandelkow, 2016).

The development of a murine model of osmotic demyelinating syndrome (ODS) allowed to study changes incurred in extrapontine zones of the CNS and featured neuron and glial cell changes in the relay thalamic ventral posterolateral (VPL) and ventral posteromedial (VPM) nuclei before, during and after ODS induction, and characterized without immune response. There, the neuron Wallerian-type deteriorations were verified with fine structure modifications of the neuron cell body, including some nucleus topology and its nucleolus changes. Morphologic analyses showed a transient stoppage of transcriptional activities while myelinated axons in the surrounding neuropil incurred diverse damages, previously reported. Even though the regional thalamus myelin deterioration was clearly recognized with light microscopy 248 h after osmotic recovery of ODS, ultrastructure analyses demonstrated that, at that time, the same damaged parenchyma regions contained nerve cell bodies that have already reactivated nucleus transcriptions and neuroplasm translations because peculiar accumulations of fibro-granular materials, similar to those detected in restored ODS astrocytes, were revealed in these restructuring nerve cell bodies. Their aspects suggested to be accumulations of ribonucleoproteins. The findings suggested that progressive neural function's recovery in the murine model could imitate some aspects of human ODS recovery cases., info:eu-repo/semantics/published

Alzheimer's disease (AD) is characterized by the accumulation in the brain of intraneuronal aggregates of abnormally and hyperphosphorylated tau proteins and of extracellular deposits of amyloid-β surrounded by dystrophic neurites. Numerous experimental models have shown that tau pathology develops in the brain after intracerebral injection of brain homogenates or pathological tau [paired helical filaments (PHF)-tau)] from AD brains. Further investigations are however necessary to identify or exclude potential extracerebral routes of tau pathology transmission, e.g., through the intravascular route. In this study, we have analyzed the effect of intravenous injection of PHF-tau proteins from AD brains on the formation of tau and amyloid pathologies in the brain of wild-type (WT) mice and of 5XFAD mice (an amyloid model). We observed that 5XFAD mice with a disrupted blood-brain barrier showed increased plaque-associated astrogliosis, microgliosis, and increased deposits of Aβ40 and Aβ42 after intravenous injection of PHF-tau proteins. In addition, an increased phosphotau immunoreactivity was observed in plaque-associated dystrophic neurites. These results suggest that blood products contaminated by PHF-tau proteins could potentially induce an exacerbation of neuroinflammation and AD pathologies.

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Synaptojanin 1 (SYNJ1) is a brain-enriched lipid phosphatase critically involved in autophagosomal/endosomal trafficking, synaptic vesicle recycling and metabolism of phosphoinositides. Previous studies suggest that SYNJ1 polymorphisms have significant impact on the age of onset of Alzheimer's disease (AD) and that SYNJ1 is involved in amyloid-induced toxicity. Yet SYNJ1 protein level and cellular localization in post-mortem human AD brain tissues have remained elusive. This study aimed to examine whether SYNJ1 localization and expression are altered in post-mortem AD brains. We found that SYNJ1 is accumulated in Hirano bodies, plaque-associated dystrophic neurites and some neurofibrillary tangles (NFTs). SYNJ1 immunoreactivity was higher in neurons and in the senile plaques in AD patients carrying one or two ApolipoproteinE (APOE) ϵ4 allele(s). In two large cohorts of APOE-genotyped controls and AD patients, SYNJ1 transcripts were significantly increased in AD temporal isocortex compared to control. There was a significant increase in SYNJ1 transcript in APOEϵ4 carriers compared to non-carriers in AD cohort. SYNJ1 was systematically co-enriched with PHF-tau in the sarkosyl-insoluble fraction of AD brain. In the RIPA-insoluble fraction containing protein aggregates, SYNJ1 proteins were significantly increased and observed as a smear containing full-length and cleaved fragments in AD brains. In vitro cleavage assay showed that SYNJ1 is a substrate of calpain, which is highly activated in AD brains. Our study provides evidence of alterations in SYNJ1 mRNA level and SYNJ1 protein degradation, solubility and localization in AD brains., SCOPUS: ar.j, info:eu-repo/semantics/published

Resume Objectif Le nombre de Drives a predominance alimentaire connait une progression fulgurante entre les annees 2010 et 2013, revolutionnant la culture de la grande distribution. Dans un contexte de defi economique, les enseignes repensent la conception des locaux et l’organisation du travail tout en minimisant les surcouts. Un Drive se definit par des points de retraits proposes par les enseignes de la grande distribution qui permettent la livraison des articles dans le coffre du vehicule du client. Il effectue au prealable une commande a distance sur un site Internet dedie ou une application mobile. Le client choisit le jour et le creneau horaire pour le retrait de ses articles. L’eclosion dans l’urgence de ces Drives interroge quant aux conditions de travail et aux consequences pour la sante-securite des salaries. Methodes Pour repondre a ces questions, deux outils complementaires sont deployes : une approche ergonomique pour analyser l’activite reelle des salaries dans les differentes enseignes et un auto-questionnaire passe aupres des preparateurs. L’objectif de l’etude ergonomique vise a identifier les contraintes de l’activite realisee et a preciser leurs determinants. L’autoquestionnaire apporte des renseignements complementaires sur les caracteristiques de la population, les douleurs evoquees et leurs ressentis quant aux contraintes physiques et psycho-organisationnelles. Resultats Les resultats montrent une population caracterisee par sa jeunesse, sa faible anciennete et son niveau de diplome eleve. Les plaintes exprimees sont importantes et affectent plus specifiquement la region lombaire, l’articulation de l’epaule et les membres inferieurs, ceci independamment des modeles de Drives. Au-dela des facteurs biomecaniques, cette approche souligne l’importance des facteurs psycho-organisationnels dans l’evocation des plaintes. Par ailleurs, cette etude ne montre pas de differences tant pour les contraintes physiques que psycho-organisationnelles entre les differents modeles de Drives. Conclusion Cette etude ouvre des perspectives d’amelioration des conditions de travail sur differents axes : organisationnel, materiel, dimensionnel et relationnel.

The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood–brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24 hr post-correction, and reached type D at 48 hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS., SCOPUS: ar.j, info:eu-repo/semantics/published

Impaired adult hippocampal neurogenesis has been reported as a feature of Alzheimer's disease and other tauopathies and might contribute to defects in learning and memory in these diseases. To assess the interference of tau pathology, a common key-lesion in these diseases, with adult hippocampal neurogenesis we analyzed adult neurogenesis in the hippocampal dentate gyrus in wild-type mice, Tg30 mice expressing a FTDP-17 mutant tau and the same Tg30 mice deficient for mouse tau (Tg30/tauKO). The volume of the granular layer, the number of granule cells and of neuronal precursors expressing the immature markers DCX or 3R-tau were analyzed in the dentate gyrus (DG) using unbiased stereological methods. The co-localization of neurogenic markers with the human mutant tau was also analyzed. We observed a significant reduction of the volume of the granular layer and of granule cells number in mutant tau Tg30 mice, but not in Tg30/tauKO mice. The number of neuronal precursors expressing the immature markers DCX or 3R-tau (the latter only expressed in wild-type and Tg30 mice) and the number of cells expressing the proliferation marker Ki-67 in the neurogenic subgranular zone of the DG was reduced in Tg30 but not in Tg30/tauKO mice. The density of phosphotau positive cells in the DG and the level of soluble human phosphotau was lower in Tg30/tauKO compared to Tg30 mice. The human mutant tau was expressed in mature granule cells in Tg30 and Tg30/tauKO mice but was not expressed in Sox2 positive neural stem cells and in DCX positive neuronal precursors/immature newborn neurons. These results demonstrate an impairment of adult hippocampal neurogenesis in a FTDP-17 mutant tau mice resulting from a decrease of proliferation affecting the pool of neuronal precursors. The mutant tau was not expressed in precursors cells in these mutant tau mice, suggesting that this neurogenic defect is cell non-autonomous. Interestingly, expression of endogenous wild-type tau in mature granule cells was necessary to observe this toxic effect of human mutant tau, since this impaired adult neurogenesis was rescued by lowering tau expression in Tg30/tauKO mice. These observations suggest that development of tau pathology in granule cells of the dentate gyrus is responsible for reduction of adult hippocampal neurogenesis also in human tauopathies by impairing proliferation of neuronal precursors, and that reduction of tau expression might be an approach to rescue this impairment.

A murine model used to investigate the osmotic demyelination syndrome (ODS) demonstrated ultrastructural damages in thalamus nuclei. Following chronic hyponatremia, significant myelinolysis was merely detected 48 h after the rapid reinstatement of normonatremia (ODS 48 h). In ODS samples, oligodendrocytes and astrocytes revealed injurious changes associated with a few cell deaths while both cell types seemed to endure a sort of survival strategy: (a) ODS 12 h oligodendrocytes displayed nucleoplasm with huge heterochromatic compaction, mitochondria hypertrophy, and most reclaimed an active NN cell aspect at ODS 48 h. (b) Astrocytes responded to the osmotic stress by overall cell shrinkage with clasmatodendrosis, these changes accompanied nucleus wrinkling, compacted and segregated nucleolus, destabilization of astrocyte-oligodendrocyte junctions, loss of typical GFAP filaments, and detection of round to oblong woolly, proteinaceous aggregates. ODS 48 h astrocytes regained an active nucleus aspect, without restituting GFAP filaments and still contained cytoplasmic proteinaceous deposits. (c) Sustaining minor shrinking defects at ODS 12 h, neurons showed slight axonal injury. At ODS 48 h, neuron cell bodies emerged again with deeply indented nucleus and, owing nucleolus translational activation, huge amounts of polysomes along with secretory-like activities. (d) In ODS, activated microglial cells got stuffed with huge lysosome bodies out of captures cell damages, leaving voids in interfascicular and sub-vascular neuropil. Following chronic hyponatremia, the murine thalamus restoration showed macroglial cells acutely turned off transcriptional and translational activities during ODS and progressively recovered activities, unless severely damaged cells underwent cell death, leading to neuropil disruption and demyelination., SCOPUS: ar.j, info:eu-repo/semantics/published

Neuropathological analysis in Alzheimer's disease (AD) and experimental evidence in transgenic models overexpressing frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) mutant tau suggest that amyloid-β pathology enhances the development of tau pathology. In this work, we analyzed this interaction independently of the overexpression of an FTDP-17 mutant tau, by analyzing tau pathology in wild-type (WT), 5xFAD, APP-/- and tau-/- mice after stereotaxic injection in the somatosensory cortex of short-length native human AD-PHF. Gallyas and phosphotau-positive tau inclusions developed in WT, 5xFAD, and APP-/- but not in tau-/- mice. Ultrastructural analysis demonstrated their intracellular localization and that they were composed of straight filaments. These seeded tau inclusions were composed only of endogenous murine tau exhibiting a tau antigenic profile similar to tau aggregates in AD. Insoluble tau level was higher and ipsilateral anteroposterior and contralateral cortical spreading of tau inclusions was more important in AD-PHF-injected 5xFAD mice than in WT mice. The formation of large plaque-associated dystrophic neurites positive for oligomeric and phosphotau was observed in 5xFAD mice injected with AD-PHF but never in control-injected or in non-injected 5xFAD mice. An increased level of the p25 activator of CDK5 kinase was found in AD-PHF-injected 5xFAD mice. These data demonstrate in vivo that the presence of Aβ pathology enhances experimentally induced tau seeding of endogenous, wild-type tau expressed at physiological level, and demonstrate the fibrillar nature of heterotopically seeded endogenous tau. These observations further support the hypothesis that Aβ enhances tau pathology development in AD through increased pathological tau spreading., SCOPUS: ar.j, info:eu-repo/semantics/published

Mechanisms driving cognitive improvements following nuclear receptor activation are poorly understood. The peroxisome proliferator–activated nuclear receptor alpha (PPARα) forms heterodimers with the nuclear retinoid X receptor (RXR). We report that PPARα mediates the improvement of hippocampal synaptic plasticity upon RXR activation in a transgenic mouse model with cognitive deficits. This improvement results from an increase in GluA1 subunit expression of the alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, eliciting an AMPA response at the excitatory synapses. Associated with a two times higher PPARα expression in males than in females, we show that male, but not female, PPARα null mutants display impaired hippocampal long-term potentiation. Moreover, PPARα knockdown in the hippocampus of cognition-impaired mice compromises the beneficial effects of RXR activation on synaptic plasticity only in males. Furthermore, selective PPARα activation with pemafibrate improves synaptic plasticity in male cognition-impaired mice, but not in females. We conclude that striking sex differences in hippocampal synaptic plasticity are observed in mice, related to differences in PPARα expression levels., SCOPUS: ar.j, info:eu-repo/semantics/published

In Alzheimer disease, the development of tau pathology follows neuroanatomically connected pathways, suggesting that abnormal tau species might recruit normal tau by passage from cell to cell. Herein, we analyzed the effect of stereotaxic brain injection of human Alzheimer high-molecular-weight paired helical filaments (PHFs) in the dentate gyrus of wild-type and mutant tau THY-Tau22 mice. After 3 months of incubation, wild-type and THY-Tau22 mice developed an atrophy of the dentate gyrus and a tau pathology characterized by Gallyas and tau-positive grain-like inclusions into granule cells that extended in the hippocampal hilus and eventually away into the alveus, and the fimbria. Gallyas-positive neuropil threads and oligodendroglial coiled bodies were also observed. These tau inclusions were composed only of mouse tau, and were immunoreactive with antibodies to 4R tau, phosphotau, misfolded tau, ubiquitin, and p62. Although local hyperphosphorylation of tau was increased in the dentate gyrus in THY-Tau22 mice, the development of neurofibrillary tangles made of mutant human tau was not accelerated in the hippocampus, indicating that wild-type human PHFs were inefficient in seeding tau aggregates made of G272V/P301S mutant human tau. Our results indicate thus that injection of human wild-type Alzheimer PHF seeded aggregation of wild-type murine tau into an argyrophilic 4R tau pathology, and constitutes an interesting model independent of expression of a mutant tau protein.

Hyperphosphorylation and fibrillar aggregation of the microtubule-associated protein tau are key features of Alzheimer's disease and other tauopathies. To investigate the involvement of tau phosphorylation in the pathological process, we generated a pair of complementary phosphomutant tau knockin mouse lines. One exclusively expresses phosphomimetic tau with 18 glutamate substitutions at serine and/or threonine residues in the proline-rich and first microtubule-binding domains to model hyperphosphorylation, whereas its phosphodefective counterpart has matched alanine substitutions. Consistent with expected effects of genuine phosphorylation, association of the phosphomimetic tau with microtubules and neuronal membranes is severely disrupted in vivo, whereas the phosphodefective mutations have more limited or no effect. Surprisingly, however, age-related mislocalization of tau is evident in both lines, although redistribution appears more widespread and more pronounced in the phosphomimetic tau knockin. Despite these changes, we found no biochemical or immunohistological evidence of pathological tau aggregation in mice of either line up to at least 2 years of age. These findings raise important questions about the role of tau phosphorylation in driving pathology in human tauopathies., SCOPUS: ar.j, info:eu-repo/semantics/published

La progression rapide du nombre de Drives alimentaires entre 2010 et 2013 interrogeait sur la possibilite de travailler dans la duree avec des conditions de travail contraignantes. Pour repondre a ce questionnement les preparateurs de commandes de la region Grand-Est sont interroges a deux ans d’intervalle (T1 = 2015/2016 et T2 = 2017/2018) par auto-questionnaire (douleurs evoquees, contraintes physiques et psycho-organisationnelles). Des scores sont construits pour mesurer les contraintes physiques et psycho-organisationnelles. En 2015, les resultats ont montre une population caracterisee par sa jeunesse, sa faible anciennete et majoritairement diplomee BAC et plus. Les plaintes exprimees etaient importantes et affectaient plus specifiquement la region lombaire, l’articulation de l’epaule et les membres inferieurs. Au-dela des facteurs biomecaniques, l’importance des facteurs psycho-organisationnels etait evoquee. En 2017, seule la moitie des salaries interroges lors de la premiere phase est encore presente. L’analyse des salaries perdus de vue montre qu’il s’agit principalement de depart pour fin de contrat. Les conditions de travail et leur vecu ne semblent pas etre a l’origine des departs. Les comparaisons de tous les salaries presents en T1 (n = 279) et en T2 (n = 446) montrent que : – les caracteristiques des preparateurs sont semblables, a l’exception du niveau de diplome, en T2 une majorite de salaries a un BAC/BAC Professionnel ; – les scores de contraintes sont identiques et la contrainte physique reste a un niveau tres eleve (T1 : 74,7/100 T2 : 75,9/100) ; – le nombre de problemes articulaires declare reste stable : en moyenne 2,7 articulations douloureuses en T1 vs 2,9 en T2. L’analyse des 105 salaries presents aux deux temps de l’etude (apparies) nuancent ces resultats : – leurs caracteristiques different de celles des nouveaux repondants (plus âges, moins diplomes, plus de CDI, femmes) ; – leurs scores de contraintes physiques sont plus eleves en T2 qu’en T1 et la frequence de la penibilite ressentie est plus importante significativement pour les contraintes biomecaniques ; – leurs scores de contraintes psycho-organisationnelles sont egalement plus eleves en T2 qu’en T1, avec en particulier une degradation du sens du travail ; – le nombre de problemes articulaires quant a lui evolue significativement : en moyenne 3,0 articulations douloureuses en T1 vs 3,7 en T2. Cette etude montre l’absence d’amelioration des conditions de travail dans les drives qui restent extremement exigeantes. Elles semblent se traduire par une apparition precoce des problemes osteo-articulaires dans une population pourtant jeune.

Dans un contexte de developpement rapide des Drives a predominance alimentaire, les equipes sante-travail se sont interrogees sur les conditions de travail de cette nouvelle activite par rapport au metier traditionnel des Employes Libre-Service (ELS) des grandes surfaces. L’objectif est de comparer les effets sur la sante de ces deux activites sur la base d’un meme auto-questionnaire (douleurs evoquees, expositions physiques et contraintes psycho-organisationnelles). Des scores sont construits pour mesurer les contraintes physiques et psycho-organisationnelles. Tous les preparateurs de commandes des drives de 34 grandes surfaces adherentes a 4 Services de Sante au Travail de la region Grand-Est (n = 446) et des ELS (n = 396 tires au sort dans ces commerces parmi les moins de 50 ans) ont ete interroges en 2017. Toutes les caracteristiques populationnelles different : les preparateurs des drives sont plus jeunes que les ELS (28,1 ans ± 8,2 vs 33,3 ans ± 9,1), moins souvent en couple/avec enfants, en CDI, a temps plein et avec une plus faible anciennete au poste. Ils sont plus nombreux a avoir un diplome BAC ou plus. En ajustant sur l’âge et le genre, le score de contraintes physiques est plus important chez les salaries des drives que chez les ELS (OR = 1,69 IC [1,27-2,26]). Les preparateurs des drives rapportent significativement plus souvent que les ELS : – des efforts/ports de charges lourdes (OR = 1,78 [1,25-2,54]) ; – d’importants deplacements a pied (OR = 3,95 [2,29-6,84]). Le score de contraintes psycho-organisationnelles est cote plus fortement par les salaries des drives que par les ELS (OR = 1,345 [1,003-1,805]). En regardant les composantes de ce score : – l’organisation du travail semble plus defavorable pour les preparateurs de commandes que pour les ELS (OR = 1,83 IC [1,35-2,47]) ; – les relations de travail semblent plus favorables pour les preparateurs de commandes que pour les ELS (OR = 0,63 IC [0,47-0,85]). La derniere partie de l’analyse porte sur l’etat de sante. Aucune difference (p = 0,5) n’est retrouvee pour les douleurs osteo-articulaire entre les salaries des drives et les ELS (respectivement 3,1 articulations douloureuses en moyenne versus 3,0). Le reclassement d’un ELS, pour restriction d’aptitude en lien avec des troubles osteoarticulaires, au poste de preparateur au drive n’est pas pertinent en raison des contraintes physiques et organisationnelles plus importantes dans ce dernier. A l’inverse, le reclassement d’un preparateur au drive vers le poste d’ELS doit s’evaluer au cas par cas en raison d’un niveau de contraintes eleve a ce poste dans certains rayons. Seule l’affectation a un secteur ou l’activite est moins sollicitante peut s’envisager.

Introduction Malgre le travail engage depuis 1995 entre la profession et le reseau prevention, les differents services de prevention constatent encore des problematiques recurrentes de conditions de travail sur le terrain. Afin d’accompagner les entreprises du secteur de la grande distribution, un groupe de travail regional constitue de differents partenaires de la prevention met en œuvre un plan d’action specifique depuis 2012. Objectifs Delivrer un message commun de prevention par les differents partenaires, orienter les priorites en matiere de prevention dans les differents metiers du secteur, former les acteurs internes a la prevention des risques, donner des outils aux entreprises pour faciliter la maitrise des risques. Methodologie utilisee Creation d’un groupe de travail pluridisciplinaire et pluri-partenarial dedie au secteur et compose d’ingenieurs et controleurs de prevention, d’ergonomes, de medecins du travail et de techniciens en prevention de la CARSAT Alsace Moselle, de la DIRECCTE Grand Est et de plusieurs SIST (ACST, AST67, AGESTRA). Le groupe de travail capitalise ses competences et son experience pour le deploiement d’actions ciblees, definit les objectifs prioritaires de prevention, travaille sur plusieurs moyens d’implication des differents acteurs concernes de l’entreprise. Actions et resultats Realisation d’une enquete longitudinale pour apprehender la perception des conditions de travail des salaries des drives et realisation d’etudes de postes dans plusieurs enseignes, – edition de brochures, une regionale d’information a destination du secteur d’activite, une ciblee sur les TMS dans les drives a destination des salaries, definition de 26 actions prioritaires a mettre en œuvre par les enseignes,- Deploiement de formations pour les enseignants des filieres ventes en partenariat avec l’Education Nationale, pour les encadrants et les instances representatives du personnel des entreprises, creation d’une formation des salaries, encadrants et futurs embauches, via la realite virtuelle, en partenariat avec l’INSA de Strasbourg, capitalisation des moyens de prevention existants dans une boite a outils pour les preventeurs. Conclusion Les actions s’inscrivent dans une demarche sur la duree et le groupe de travail est rejoint par de nouveaux partenaires (STSA, SIST Centre Alsace). Il permet un discours commun de prevention par les acteurs externes de l’entreprise dont les roles et les approches peuvent differer. Le travail en pluridisciplinarite est un levier pour faire progresser un secteur d’activite en constante mutation et marque par une sinistralite elevee.

Recent innovations in tissue clearing and imaging technologies have enabled us to analyse biological systems directly in three-dimensions using thick samples. In this review, we discuss two of these recently reported tissue-clearing technologies (CLARITY and CUBIC) that are compatible with archival formalin-fixed human brain materials that have been fixed in formalin for a long period of time. We will discuss the pros and cons of these two technologies, examples of visualisation of Alzheimer neuropathological hallmarks and the exact protocols that we regularly use in the laboratory.

Abeta deposits and tau pathology were investigated in 24 French patients that died from iatrogenic Creutzfeldt-Jakob disease after exposure to cadaver-derived human growth hormone (c-hGH) in the 1980s. Abeta deposits were found only in one case that had experienced one of the longest incubation periods. Three cases had also intracellular tau accumulation. The analysis of 24 batches of c-hGH, produced between 1974 and 1988, demonstrated for the first time the presence of Abeta and tau contaminants in c-hGH (in 17 and 6 batches, respectively). The incubation of prion disease was shorter in the French patients than the incubation times reported in two previously published British series. We interpreted the low incidence of Abeta in this French series as a consequence of the shorter incubation period observed in France, as compared to that observed in the United Kingdom. This concept suggested that a mean incubation period for the development of detectable Abeta deposits would be longer than 18 years after the first exposure. Moreover, we hypothesized that tau pathology might also be transmissible in humans.