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Iskandar, Samy. "Développement de formes vectorisables innovantes dans le cadre de maladies liées à l'âge". Thesis, Aix-Marseille, 2019. http://theses.univ-amu.fr.lama.univ-amu.fr/191211_ISKANDAR_942qv952dpkqb571ugya506omy_TH.pdf.
Pełny tekst źródłaAlzheimer's disease is a degenerative brain disease where abnormal chemicals accumulate causing progressive deterioration of memory and intellectual ability. It is a neurodegenerative disease that causes lesions in the brain. Irreversible lesions lead to a decline in cognitive functions, which serve to process information, and behavioral as the disease progresses. Loss of immediate memory, and then older memories, changes in judgment and reasoning, changes in mood and behavior are the main manifestations.Contrary to popular belief, Alzheimer's disease is not related to the normal aging of the brain. Today, the cost of the disease in Europe is estimated at 160 million euros/year, despite that, there is no effective symptomatic treatment.New non-drug approaches should be explored to slow the progression of the disease. Research in the field of the "Drug Delivery System" reveals increasingly promising systems. Addressing molecules of therapeutic interest to a target tissue is a major challenge in Drug Delivery. New targeting technologies have emerged. The search for vectors having a sufficiently long life in the body to reach the target area has already been put in place. This work is a modest step in the exploration of nanovectorized herbal medicine for the treatment of Alzheimer's disease
Gardette, Virginie. "Étude de l'utilisation des médicaments dans la maladie d'Alzheimer et maladies apparentées". Toulouse 3, 2013. http://www.theses.fr/2013TOU30277.
Pełny tekst źródłaThe leading cause of dementia is Alzheimer's Disease (AD). To date, the drugs marketed in AD (cholinesterase inhibitors and memantine, also called antidementia drugs) are symptomatic and of limited efficacy. In particular, the optimal treatment duration is still under debate. In addition, neuroleptics (antipsychotics) are commonly used in behavioural and psychological symptoms of dementia (BPSD). However, their use remains mostly off label and an increased mortality risk has been suggested with these agents. This led to 2 warnings in march 2004 and December 2008 issued by the French drug agency (AFSSaPS). Data about longitudinal drug use's patterns among clinically confirmed AD patients in a real-life setting remain scarce. This thesis dealt with pharmacoepidemiologic studies of antidementia drugs and antipsychotics is subjects with Alzheimer's Disease or associated disorders. The first part of this thesis aimed to (i) estimate the incidence of antidementia drugs' discontinuation and switch, and (ii) to identify predictive factors of these 2 outcomes. We conducted 2 researches in 2 cohorts. The first analysis was conducted among 611 French AD patients followed for 2 years. The second analysis was performed among a European cohort of 1375 subjects with AD followed for 2 years. We restricted this analysis to the antidementia drugs new users (n=557). The second part of this thesis aimed to study antipsychotic drug use in AD and associated disorders. We first studied the mortality risk associated with antipsychotic use in a 4-year cohort of 686 French subjects with AD. We secondarily described trends in the use of antipsychotic drugs in France between 2003 and 2011, and assessed the impact of AFSSaPS warnings. To this aim, we conducted an interrupted time series study among subjects with and without dementia in the French main Health Insurance Scheme. Patterns of drug use and proper use of medicinal drugs in AD need to be further investigated
Grznárová, Katarína. "Les relations moléculaires entre la maladie d'Alzheimer et les maladies à prions". Paris 7, 2013. http://www.theses.fr/2013PA077291.
Pełny tekst źródłaMany human neurodegenerative diseases are now considered as caused by protein misfolding and prion-like mechanisms seem to be more the rule in these processes than an exception limited to prion diseases. The normal prion protein (PrP) appears to be critical in neurodegeneration induced by Aβ oligomers in Alzheimer's disease (AD). However, PrP- Aβ interaction is not reserved only to toxic Aβ1-42 oligomers. Also monomeric Aβ1-40, naturally produced in healthy brain as non-aggregated peptides, have been shown to interact with cellular PrP. We explored here the role of the interaction between PrP and monomeric Aβ1-40 in PrP aggregation process. To this aim, PrP and Aβ1-40 were produced as highly pure and monodisperse recombinant proteins. We show here a clear positive effect of Aβ1-40 on PrP aggregation. Moreover, we demonstrate that Aβ1-40 naturally binds to two distinct N-terminal regions of PrP and subsequently to a third binding site created after structural rearrangement of PrP globular domain, which contributes to enhance the oligomerization rate of the complex. These results bring new insight into the mechanisms of the physiologically relevant PrP-Aβ1-40 interaction as well as into key structural changes that might be involved in prion diseases
Quoniam, Nolwenn. "L'apathie dans la maladie d'Alzheimer et la démence fronto-temporale". Paris 5, 2007. http://www.theses.fr/2007PA05H048.
Pełny tekst źródłaThis thesis examined mechanisms of apathy in Alzheimer's disease (AD) and fronto-temporal dementia (FTD). Therefore we included 36 AD, 13 FTD and 29 control subjects. Results showed different profiles of apathy depending on the pathology : among the FTDs, apathy was global, involving all activity fields, whereas among the Ads, apathy was selective, involving only some activity field. Each of these apathy profiles was related to different psycho-affective and behavioural disturbances. The FTDs showed dysexecutive syndrome related with frontal behavioural troubles. On the contrary, ADs showed less important executive and frontal perturbations related to other troubles (depression) that do no exist among the FTDs. Apathy seemed related with organic mechanisms (because evolving with the intensity of the cognitive deficiency) and/or psycho-affective mechanisms (depression, anxiety due to repeated failures)
Costes, Ghyslaine. "Les anticholinestérasiques dans la maladie d'Alzheimer". Bordeaux 2, 1999. http://www.theses.fr/1999BOR2P057.
Pełny tekst źródłaPariente, Antoine. "Impact des inhibiteurs de l'acétylcholinestérase dans la maladie d'Alzheimer et les maladies apparentées". Bordeaux 2, 2008. http://www.theses.fr/2008BOR21574.
Pełny tekst źródłaMore than 850 000 persons are affected by Alzheimer's disease (AD) and other dementias in France. The clinical meaning of the efficacy of cholinesterase inhibitors (Ch1s) in these indications remains controversial. The objective of this thesis was to estimate the impact of Ch1s in population in the treatment of AD and other dementias. Firstly, we studied the use of Ch1s in the population : 20 % of demented patients could use Ch1s in France, among whom 45 % would present one-year persistence to treatment, the persistence being lower for older or paucisymptomatic patients. These factors could thus lmit the potential impact of Ch1s. Secondly, we studied the efficacy of Ch1s in the population : Ch1 use, without considering its patterns, was not associated with a decreased risk of rapid cognitive decline. Conversely in treated patients, non-persistence was associated with a two-fold increase in the risk of institutionalisation or death. Ch1s could thus have a clinically meaningful efficacy providing that their patterns of use warrant a sufficient persistence. Thirdly, we studied the safety of Ch1s in the population : the risk of severe adverse events, among all events, was higher for patients treated with Ch1s using psychotropics. The use of antipsychotics was associated with an increased risk of myocardial infarction, without any interaction with the use of Ch1. These results could help reconsidering the interest of Ch1s in the treatment of AD and other dementias. They also allowed to identify the populations in which the patterns of use of Ch1s were the most likely to compromise their therapeutic benefit and should be optimized to improve the impact of these drugs
Loiseau, Valérie. "La maladie d'Alzheimer : à la recherche d'une stratégie thérapeutique". Bordeaux 2, 1995. http://www.theses.fr/1995BOR2P090.
Pełny tekst źródłaWallon, David. "Phénotypes de la maladie d'Alzheimer génétiquement déterminée et identification de nouvelles causes". Rouen, 2014. http://www.theses.fr/2014ROUENR01.
Pełny tekst źródłaOur objective was to study the phenotypes and genetic abnormalities related to early-onset Alzheimer Disease. The proportion of mutations leading to an autosomal dominant inheritance was: 51% for PSENT, 6% for PSEN2, 11% of APP mutations and 9% of APP duplications. The limits and means (m) of the age of onset were respectively: [24-63 years] (m=43. 6); [53-69] (m=55. 9); [35-61] (m=50. 8) and [41-65] (m=51. 3). Classical AD was the main phenotype (82%) but in 18% of cases, the phenotype was atypical Among patients harboring PSEN1 mutations, we described spastic paraplegia (14. 8%), frontal variant (10. 8%), ataxia (5. 4%) or early seizures (19. 6%). Seizures were more frequent in APP duplications (31. 2%). The cerebrospinal fluid (CSF) biomarkers were indicative of AD in 90% of these patients. In case of discrepancy between clinical and biomarker conclusions, 76. 9% of clinicians changed their final diagnosis according to the CSF biomarkers. However, a limit of these biomarkers was illustrated since we found 2. 6% of patients harboring a hexanucleotidic expansion of C90RF72 among 114 patients with early onset dementia and CSF biomarkers indicative of AD. According to our algorithm, 18% of familial EOAD cases (age of onset (A00) before 65 years) and 14% of sporadic cases (MO before 50 years) were related to an APOE4/E4 genotype. Twenty-three percent of 168 families and 66% of 81 sporadic cases remained negative for these 3 genes and were enrolled in a pangenomic research program. Four familial and 3 sporadic cases were reported harboring copy number variants of several new genes involved in the amyloid cascade. Using next generation sequencing, 7 out of 29 unrelated familial cases harbored mutations of SORL1. Fourteen sporadic cases with combined analyses of their healthy parents allowed us to discover de novo mutations in genes related to amyloid or Tau-protein. Functional tests and large case-control studies are in progress in order to propose these genes to molecular diagnosis
Alleaume-Butaux, Aurélie. "Des maladies à prions à la maladie d'Alzheimer : vers l'identification de mécanismes communs de neurodégénérescence". Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB100.
Pełny tekst źródłaPas de résumé en anglais
Song, Pu Jiao. "Apport de l'imagerie moléculaire de la neurodégénérescence : des maladies à prion à la maladie d'Alzheimer". Tours, 2008. http://www.theses.fr/2008TOUR3317.
Pełny tekst źródłaSong, Pujiao. "Apport de l'imagerie moléculaire de la neuro-dégénérescence : des maladies à prion à la maladie d'alzheimer". Thesis, Tours, 2008. http://www.theses.fr/2008TOUR3102.
Pełny tekst źródłaPons, Vincent. "Rôle du CSF1R dans les maladies neurodégénératives". Doctoral thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/68078.
Pełny tekst źródłaGuillemaud, Océane. "Hétérogénéité de la réactivité astrocytaire dans la maladie d'Alzheimer". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL003.
Pełny tekst źródłaAstrocytes are essential for brain function. In Alzheimer’s disease (AD), astrocytes become reactive. The role of reactive astrocyte (RA) in AD is still debated. We used a viral approach to selectively modulate RA in vivo, by targeting the JAK2-STAT3 pathway in two AD mouse models. We report deleterious effects of RA on amyloid pathology and spatial learning in APP/PS1dE9 mice (Ceyzériat et al., 2018). In 3xTg-AD mice, the modulation of RA improves synaptic transmission and plasticity but has nos effect on amyloid and Tau pathologies or spatial memory (Guillemaud et al., 2019). These results suggest that RA have variable effets in disease and acquire context-dependent molecular and functional changes (Escartin et al., 2019). The signaling cascades controlling RA diversity have not yet been identified. Our goal was to study the transcriptional profile and functional features of different classes of reactive astrocytes identified by their signaling cascades, in the prefrontal cortex of APP/PS1dE9 mice. We found that the STAT3 and NF-κB pathways are activated heterogeneously and defines molecularly and functionally different classes of RA. Overall, this project demonstrates the complexity of RA in AD and validates new tools to studying RA heterogeneity
Masse-Desrosiers, Michelle. "Le rôle des travailleurs sociaux en collaboration interprofessionnelle auprès des personnes atteintes de la maladie d'Alzheimer ou d'autres maladies apparentées". Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/28105.
Pełny tekst źródłaThrough sustained efforts to establish a professional role and to develop its own psychosocial and ecological perspectives, meaningful contributions from social work are likely to improve the quality of life of people with Alzheimer's disease and related conditions and their families. However, the role of the social worker in the interprofessional teams is not sufficiently clarified and this seems to cause confusion among the clientele and other professionals. This qualitative study, which is exploratory and descriptive in nature, aims to better understand social workers' perception of their roles in people with Alzheimer's disease or a related condition and the challenges of these roles in interprofessional collaboration. The analysis of the semi-structured individual interviews with 10 participants demonstrated that the definition and contribution of social workers within interprofessional teams remains to be clarified. It was possible to document the role of social workers and to identify three role issues: ambiguity, conflict and role overload, despite a limited number of participants.
Masse, Isabelle. "Les agents hypolipémiants (fibrates, statines) : approche expérimentale et clinique des effets protecteurs dans les pathologies ischémiques et dégénératives". Lille 2, 2006. http://www.theses.fr/2006LIL2S048.
Pełny tekst źródłaBest knowledge of metabolic pathway involved in Alzheimer and stroke pathogenesis leads to new therapeutic approach to induce neuroprotection. The pleiotropic effects, such as anti-inflammatory or anti-oxidants effects, were described for lipid lowering agents (LLAs). First we investigate in an observational study whether LLAs are associated with a slower cognitive decline in Alzheimer's disease. Patients treated with lipid lowering agents had a slower decline on the MMSE (1. 5/year, p=0. 0102) than patients with untreated dyslipemia (2. 4), or normolipemic patients (2. 6). Patients with a slower decline were more likely to be treated with LLAs. Logistic regression analysis, with low annual cognitive decline as dependant variable, showed that the independent variable LLAs was positively associated with the probability of lower cognitive decline (OR=0. 45, p=0. 002). Second, we aim to determine clinical and pharmacological factors taht could influence the initial severity and short term outcom of cerebral ischemia. 362 consecutive patients were included in a cross-sectional hospital-based study of patients with acute ischemic stroke. Independent factors associated with a lower severity measured on the NIH scale at admission were previous leisure-time physical activity (OR=1. 67), TIA (OR=2. 28) and treatment with lipid lowering agents (OR=1. 76). Third, 1 week after reperfusion, we observed in rats submitted to cerebral ischemia, appearance of amyloid peptide immunoreactivity associated with decreased performance on place recognition task of Y-maze. Fenofibrate allows to prevent partially these alterations : a trend for decreased cognitive impairment and amyloid peptide immunoreactivity and a significant reduction of infarct size
Kashani, Alireza. "Les transporteurs vésiculaires du glutamate, VGLUT1 et VGLUT2, dans les maladies de Parkinson et d'Alzheimer". Paris 12, 2006. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990002323940204611&vid=upec.
Pełny tekst źródłaMendez, Gomez Juan Luis. "Biomarqueurs rétiniens de la maladie d'Alzheimer et du vieillissement cérébral". Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0370/document.
Pełny tekst źródłaThe eye and central nervous system (CNS) have a common embryological origin, and easily observable retinal structures may reflect brain damage. The primary objective of this thesis was to analyze the relationship between retinal disorders and clinical (cognitive decline, dementia) and para-clinical (brain imaging) brain aging manifestations. Two types of retinal "biomarkers" were analyzed: the retinal nerve fiber layer (RNFL) and vascular structures. The data used come from the population-based cohort 3-Cities Alienor. We have shown that subjects with reduced RNFL thickness (measured by spectral-domain optical coherence tomography, SD-OCT) showed a reduced episodic memory score (cognitive function that is principally affected in Alzheimer's disease, AD) after 2 years of follow-up; over this short period of time no association with dementia risk was found. A reduced RNFL thickness was also associated with altered MRI parameters in visual pathways and in limbic system regions, which are particularly vulnerable in AD. Finally we have shown that reduced vascular choroid layer thickness was associated with larger white matter hyperintensities volumes. Vascular and neurodegenerative disease processes are associated with brain aging. Thus, alterations in the CNS by AD and brain aging could be reflected in the retina. Other research is still needed before considering the retina as a potential biomarker of brain aging
Duron, Emmanuelle. "Système IGF-1, maladie d’Alzheimer et maladies cardio-vasculaires". Paris 5, 2011. http://www.theses.fr/2011PA05T030.
Pełny tekst źródłaSince no curative treatments are available for Alzheimer’s disease (AD), focus of early risk factors and markers is of major interest. Hypertension is a risk factor for AD but the impact of antihypertensive therapy on the cognitive function in patients already diagnosed with AD is unknown. We conducted an observational study, including 321 AD outpatients (mean age: 78 years), followed-up three years with a yearly cognitive evaluation by Mini-Mental State Examination (MMSE/30). MMSE means were significantly higher among patients using antihypertensive therapy compared to those without antihypertensive therapy, after adjustment for age, gender, education level, blood pressure and MMSE at baseline (p< 0. 001)). Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) are involved in atherosclerosis and may be involved in MA pathogenesis. We assessed the relationship between IGF-1, and IGFBP-3 (ELISA) serum levels and cognitive impairment. In this cross-sectional study, 694 elderly subjects (mean age: 78. 6 years) were included in four memory centers: 224 subjects were diagnosed with AD, 257 with Mild Cognitive Impairment (MCI) and 213 cognitively normal subjects (recruited among patients caregivers) constituted the control group. IGFBP-3 serum levels were higher in the controls as compared to the MCI and AD patients after adjusting for age, gender, educational level, and ApoE ε4 status (p<0. 05). The IGF-1 serum levels were similar between the 3 groups. The main determinants of AD were age (OR (95%CI) = 1. 11 (1. 07-1. 15)), female gender (OR (95%CI)=0. 53 (0. 31 ? 0. 90)), ApoE ε4 status (OR (95%CI)= 2. 76 (1. 68 - 4. 54)), low educational level ((OR (95%CI)= 4,73 (2. 17 - 12. 3)) and low IGFBP-3 level (OR (95%CI)= 0. 83 (0. 70 -0. 98)). These results justify a prospective study to evaluate whether IGF-1/ IGFBP-3 serum levels are determinants of progression from MCI to AD
ANCOLIO, MORCQ KARINE. "Etude phenotypique des mutations des genes associees aux formes familiales des maladies d'alzheimer et de parkinson". Nice, 2000. http://www.theses.fr/2000NICE5414.
Pełny tekst źródłaPariente, Jérémie. "Neuro-imagerie fonctionnelle, deux applications : récupération motrice après un AVC, déclin cognitif dans la maladie d'Alzheimer". Toulouse 3, 2004. http://www.theses.fr/2004TOU30180.
Pełny tekst źródłaThe aim of this work was to determine to which extent the cortical network activated during an activation paradigm was altered by serotonin reuptake inhibitor after a stroke or at an early stage of Alzheimer disease. We have shown in a double blinded placebo fMRI study that SSRIs -fluoxetine and paroxetine- were able to modulate both motricity and the motor cortical network in healthy volunteers and stroke patients. We have also investigated the neuronal substrate of the placebo effect -anterior cingulum, DLPFC and opioid system- in a PET study involving patients suffering of a chronic painful condition. Finally, we have compared in an event related fMRI study Alzheimer disease patients and matched controls while performing a paired associative learning task. We have shown that patients hyperactivated a cortical network in order to compensate for the cognitive decline
Damon, Didier. "Statut matrimonial du sujet âgé et risque de démence ou de maladie d'Alzheimer : résultats de l'enquête longitudinale Paquid". Bordeaux 2, 1997. http://www.theses.fr/1997BOR2M076.
Pełny tekst źródłaVandal, Milène. "Interrelation entre déficits métaboliques et neuropathologie associée à la maladie d'Alzheimer chez la souris 3xTg-AD". Doctoral thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/26779.
Pełny tekst źródłaLa maladie d’Alzheimer (MA) est la maladie neurodégénérative qui cause le plus important nombre de cas de démence. On estime que près de 15% des canadiens âgés de plus de 65 ans sont atteints de la MA. Avec le vieillissement de la population, le nombre de cas augmentera de manière substantielle dans les prochaines années. À l’heure actuelle, aucun traitement ne permet de ralentir la progression de la maladie. Pour plus de 99% des cas, ses causes exactes demeurent indéterminées. Toutefois, de nombreux facteurs de risque ont été identifiés. Parmi eux, on retrouve plusieurs facteurs liés au métabolisme énergétique dont l’obésité et le diabète de type 2 (DT2). De manière intéressante, des modifications du métabolisme, telles qu’une résistance à l’insuline centrale et périphérique, sont également observées chez les patients Alzheimer. Afin de mieux comprendre l’interaction entre le DT2 et la MA, nous avons d’abord étudié les altérations métaboliques chez la souris triple transgénique (3xTg-AD), un modèle murin de la MA. Nous avons, en premier lieu, observé une intolérance au glucose qui progresse avec l’âge, qui est plus importante chez les femelles et qui semble liée à l’accumulation du peptide beta-amyloïde (Aβ) humain dans le pancréas. Ensuite, nous avons nourri cette souris avec une diète riche en gras pour vérifier l’impact d’une aggravation des déficits métaboliques sur la pathologie Alzheimer. L’aggravation de l’intolérance au glucose chez les souris 3xTg-AD semblait liée à l’atrophie des îlots de Langerhans et, en conséquence, à une réduction de la production d’insuline en réponse à l’injection de glucose. En plus de l’aggravation des déficits métaboliques, la diète riche en gras a augmenté de manière drastique l’accumulation de la forme soluble du peptide Aβ dans le cortex et a déterioré la mémoire des souris 3xTg-AD. De manière intéressante, l’élévation du peptide Aβ et les troubles de la mémoire ont été rétablis par l’administration d’une seule dose d’insuline. Aussi, nous avons observé une augmentation du peptide Aβ dans le plasma 30 minutes à la suite de l’injection d’insuline, suggérant qu’il est possible que la baisse rapide du peptide soit en partie causée par une élévation de la clairance du peptide au cerveau. Ces résultats renforcent les évidences supportant le potentiel thérapeutique de l’insuline dans le traitement de la MA. Toutefois, les résultats chez les patients mettent en lumière l’inefficacité de l’administration intranasale d’insuline chez les porteurs de l’allèle 4 du gène de l’apolipoprotéine E (APOE4). Afin de comprendre les raisons qui expliquent cette différence de réponse à l’insuline chez les porteurs de l’APOE4, nous avons injecté des souris exprimant l’APOE3 et l’APOE4 humain avec de l’insuline dans le but de vérifier l’effet central et périphérique de l’insuline chez ces animaux. Les souris APOE4 montrent une plus importante élévation de la signalisation de l’insuline au cerveau comparativement aux souris APOE3. Cette plus haute réponse est aussi associée à une élévation plus importante de la phosphorylation de la protéine tau, un marqueur neuropathologique de la MA. En somme, ces résultats suggèrent qu’il existe un cercle vicieux entre la MA et le DT2. L’administration d’insuline a un potentiel thérapeutique intéressant pour la MA, malgré des effets limités chez les patients APOE4 en raison de son impact probable sur la phosphorylation de la protéine tau.
Alzheimer’s disease (AD) is the neurodegenerative disorder underlying most dementia cases. About 15% of canadians over 65 years suffer from AD. With the aging of the population, AD cases are expected to increase in years to come. Unfortunately, no treatment is able to slow down the progression of the disease. For more than 99% of the cases, the cause of the disease remain undetermined. However, several risks factors have been identified, including Type 2 Diabetes (T2D) which doubles the risk of developing AD at a later age. Interestingly, metabolic changes such as impaired peripheral and central insulin signaling were also identified in AD patients. To study the interelation between AD and diabetes, we first studied the impact of the induction of AD on peripheral metabolism in an animal model, the 3xTg-AD mouse. We found that the generation of AD neuropathology was associated to glucose intolerance, which progressed with age and was more important in females than in males. Furthermore, glucose intolerance was linked to the accumulation to human beta-amyloid peptide (Aβ) in the pancreas of 3xTg-AD mice. Next, we fed the 3xTg-AD mice a high-fat diet to see the impact of exacerbating metabolic deficits on AD-like neuropathology. The high-fat diet aggravated glucose intolerance and was linked to a reduce pancreatic islets size and impaired insulin production in response to glucose injection. Futhermore, high-fat diet was associated to an increased soluble Aβ accumulation in mice cortex as well as a deteriorated memory function. Interestingly, Aβ accumulation and memory funciton were restored with a single insulin injection. We also observed an increased plasma Aβ 30 min following insulin injection, suggesting that the peptide might be cleared from the brain following insulin administration. Those results strengthen the evidences suggesting that insulin might be an interesting therapeutical tool in AD. However, results in human patients using intranasal insulin suggest that APOE4 carrier do not benefit from insulin. To study the effect of APOE genotype on central insulin response, we injected APOE3 and APOE4 mice with a single insulin injection, five min before sacrifice. We found that APOE4 genotype was linked to a more important cerebral insulin signaling following insulin administration. Also, more increased phosphorylation of tau protein was observe in APOE4 mice injected with insulin. In summary, those results highlight the presence of a vicious circle between AD and T2D. Insulin administration might be an interesting therapeutical tool in AD, although it’s effects are limited in APOE4 patients.
Viotti, Julien. "Contribution de la fonction transcriptionnelle de la parkine dans les maladies du système nerveux central : études des maladies d'Alzheimer, de Parkinson et des cancers cérébraux". Thesis, Nice, 2014. http://www.theses.fr/2014NICE4085/document.
Pełny tekst źródłaGliomas are the most common form of brain tumor, the etiology of which remains unknown. Several epidemiological studies have shown the existence of a correlation between neurodegenerative diseases and brain tumor. We hypothesis that these two pathology share common molecular denominators. Here I study the role of parkin (PK) an ubiquitin ligase responsible of early onset Parkinson diseases. Several arguments support the involvement of PK in glioma. Studies have shown that PK expression is alterated in many types of cancers. PK is also a transcription factor which can bind to p53 DNA and inhibits its transcription. P53 is a tumor suppressor often find inactivate in cancers (50%). There is evidence of specific somatic mutations found in glioma. My work was organize according to three axes 1- PK and Alzheimer disease: PK activates préséniline 1 expression and inhibits préséniline 2. 2- PK through XBP-1 regulates p53, a transcription factor activated by reticulum stress, which in turn regulates the expression of DJ-1. 3- PK and Glioma: There is a decrease in parkin expression that can be correlated to p53 expression increase in glioma biopsies. I show that p53 is able to activate PK synthesis, a mechanism abolish by p53 mutations in tumors
Gerakis, Yannis. "Stress réticulaire et maladie d'Alzheimer : contribution du facteur de transcription XBP-1s". Thesis, Université Côte d'Azur (ComUE), 2016. http://www.theses.fr/2016AZUR4097/document.
Pełny tekst źródłaAlzheimer's disease is a neurodegenerative pathology strongly correlated to aging. Its symptoms are characterized by an impaired short term memory process in the early stages of the disease and later on by a loss of all type of memory process. There is actually no cure for this pathology. At the histo-pathological levels, the disease show an accumulation of aggregated proteins in the brain (called amyloid protein) in the intra or extra cellular space, which act as a disruptor of the normal neuronal function and activity. Thus, most of the therapeutic approach to treat the disease aim at removing those proteins aggregates from the brain. However, some of the Alzheimer's disease characteristics could be melded with normal aging : One such case is the global decrease of the proteostasis mechanism in the cell which normally happen in normal brain. The assumption made during this work is that the recovery of these mechanisms impaired by age would constitute a credible therapeutic approach, complementary to the other existing approaches to the complex disease that is Alzheimer's disease. Following this hypothesis I was interested in the role and regulation of one of the major system controlling proteostasis: the UPR (unfolded protein response), and particulary to the XBP-1s transcription factor , considered one of the master regulator of this cellular network
Rei, Damien. "Le rôle de P53 en temps qu'inducteur de mort neuronale chez les souris p25". Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX20658.
Pełny tekst źródłaFifre, Alexandre. "Mort cellulaire et maladie d'Alzheimer : mécanismes moléculaires impliqués dans l'apoptose neuronale induite par le peptide β-amyloïde (Aβ) sous forme soluble et facteurs protecteurs associés". Nancy 1, 2006. http://www.theses.fr/2006NAN11314.
Pełny tekst źródłaBuée-Scherrer, Valérie. "La phosphorylation des protéines microtubulaires tau dans la maladie d'Alzheimer : étude immunochimique d'un épitope phosphorylé. Similitudes et différences au cours du développement et d'autres maladies neurodégénératives". Lille 1, 1995. http://www.theses.fr/1995LIL10070.
Pełny tekst źródłaAuffret, Alexandra. "Caractérisation des dysfonctionnements synaptiques précoces sur des modèles animaux de maladies d'Alzheimer exprimant une mutation de la présénilile 1". Paris 5, 2009. http://www.theses.fr/2009PA05T016.
Pełny tekst źródłaAlzheimer's disease (AD) is the most common cause of dementia in the elderly characterized by amyloid plaques. Mutations in Presenilin or Amyloid Precursor Protein genes cause early-onset familial forms of AD. Familial mutations led to the creation of several transgenic mice. PS1 mutations cause the most agressive forms of Familial Alzheimer's disease. My PhD project was to study age-dependent synaptic dysfunctions on transgenic mice expressing human Presenilin 1 familial Alzheimer's disease mutations L286V or M146V. Taken together, these results support the view that PS1 mutations promote synaptic dysfunctions and underline the crucial role of PS1 during both normal and pathological aging
Pierron, Géraldine. "Les enjeux psychiques de la relation d'aide entre l'aidant familial et son proche atteint de maladie d'Alzheimer ou de maladies apparentées, lorsque le patient vit à domicile". Thesis, Besançon, 2015. http://www.theses.fr/2015BESA1013/document.
Pełny tekst źródłaIf the litterature states reservations of the family caregivers, to ask for help, their psychic springsremain badly known. Nevertheless the sense of guilt was already located, as an obstacle at the request ofhelp, of the caregiver, but this factor was little explored in a research theme. This research bases on thehypothesis that the sense of guilt of the family caregiver, would represent the main brake, susceptible toprevent his request of help and support, in front of the Alzheimer's disease or the related disease, when thepatient lives at home. A sub-hypothesis aims at placing differently the sense of guilt of the familiy caregiver,according to its spouse's position, or more widely of descendant (child, son-in-law, daughter-in-law) in therelation of help. To test this hypothesis, thirty eight semi-directive conversations were realized andcompleted by the signing of the scales of attachment (RSQ), the caregiver (CRA), and depression (Beck).This research aims at clarifying foudations, and mechanisms of the sense of guilt of the family caregivers, byarticulating it in the problem of loss, which is heart of Alzheimer's disease or the related diseases. It thusgives a new perspective on the psychic work of the family caregiver, which deviates from its only accessunder the angle of the burden and the exhaustion, to envisage it in the light of the work of the pre-mourning,which appears at the keystone of the relation of help. Consequently, the research will follow the cycle of thedependence of the patient, to release in each of its stages, the incidences of the loss in the psychic andintersubjective space at the family caregiver, according to the nature of the links of attachment developpedwith the patient, but also with the family group. From there, we shall try to connect the main register ofelaboration of the loss, in a profile of singular caregiver in the relation of help, to light the links between hisdemonstrations of guilt and his demand of help
Belarbi, Karim Ali. "Caractérisation d'un modèle murin de dégénérescence neurofibrillaire : étude de conséquences fonctionnelles de la pathologie tau potentiellement impliquées dans les phases précoces de la maladie d'Alzheimer". Lille 2, 2009. http://www.theses.fr/2009LIL2S018.
Pełny tekst źródłaSartori, Maxime Steno. "Etude in vivo de l'impact de la surexpression du gène BIN1 dans un modèle murin de la maladie d'Alzheimer". Electronic Thesis or Diss., Strasbourg, 2018. http://www.theses.fr/2018STRAJ131.
Pełny tekst źródłaLate Onset Alzheimer Disease represents more than 99% of total Alzheimer cases and it is not caused by genetic mutations. Among risk factors such as age, genetic compounds as BIN1 appear to be determinant for the pathological process establishment. This study aims to determine the BIN1 overexpression effect in mice and in a tauopathy context. In this study, BIN1 overexpression alone caused short term memory impairments linked with the cellular and molecular abnormalities. These disorders are exacerbated by a combination of TgBIN1 mice with a tauopathy model, both in males and females. Surprisingly, BIN1 overexpression rescued long term and spatial memory regarding the age and sex. Hippocampus appeared to be preserved from intracellular Tau inclusions. Moreover, fornix myelin is found intact. These elements highlighted BIN1 which is a key gene in tauopathie establishment. BIN1 neuroprotective activity is mediated by direct molecular interactions both with Tau and RTN4-A/Nogo-A
Caussade, Diane. "Troubles du langage verbal et non-verbal dans la maladie d'Alzheimer : Effets d'ateliers en voix chantée". Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAL019/document.
Pełny tekst źródłaDespite the multimodal character of language, few researches studied the verbal and non-verbal communication abilities of people with Alzheimer’s disease, and even less of remediation via singing voice of those disorders. However their remediation could help to slowing down the symptomatic progression of language disorders. Given life expectancy, the exponential prevalence of neurocognitive disorders from 65 years old – of which most frequent cause is Alzheimer’s disease for which no curative treatment exists at this time –, the identification of factors slowing the symptoms progression is of the utmost importance. In view of those elements, this research focuses on the impact of singing on verbal and non-verbal communication disorders in Alzheimer’s disease. To do so, an original protocol has been set up consisting in a repetition task in singing or in speech, with or without the presentation of communicative manual gestures. This protocol helped evaluating multimodal communication abilities of people with Alzheimer’s disease and with ‘normal’ ageing. At the pre-tests, many verbal and non-verbal language disorders have been found. From the mild stage of the disease, the participants of the Patient group have produced more linguistic errors (of different types) and pauses and/or vocalic lengthenings than Control group participants. The manual gestures repetition ability of the participants of the Patient group also seems impacted, as the quality of iconic gestures production. From the moderate stage of the disease, the participants of the Patient group have produced more linguistic errors and on different types of linguistic unities, as well as more spontaneous co-verbal gestures than Control group participants. From the severe stage of the disease, the participants of the Patient group have repeated less utterances and produced more pauses and/or vocalic lengthenings than Control group participants. An impact of singing voice has only been noted on the utterances’ repetition rate, less high in singing and speech for all participants, which could be cause by a double task effect. The comparative results of verbal and non-verbal linguistic abilities have showed a positive impact of workshops in singing on the production of linguistic errors and the communicative gestures repetition of the participants of the Patient group. Our results have been discussed in the light of literature in order to distinguish verbal and non-verbal language disorders linked to ‘normal’ ageing and those symptomatic of Alzheimer’s disease. These findings enable us to make progress and to bring contribution in the current debate on the diverse possible origins of language in its multimodality, as well as suggest a line of research of the impact of singing voice on language disorders of people with Alzheimer’s disease
Rey, Christophe. "Dysfonctionnement de l'aire CA2 de l'hippocampe et déficits de mémoire sociale dans un modèle murin de la maladie d'Alzheimer". Thesis, Toulouse 3, 2020. http://www.theses.fr/2020TOU30091.
Pełny tekst źródłaOne of the most excruciating cognitive problems observed in patients with Alzheimer's disease (AD) is their inability to recognize others. To date, the neural mechanisms underlying this form of memory, called social memory, are partly unknown. This cognitive function requires the integration of numerous sensory information and elaborated memory processes, suggesting that the hippocampal circuit may be involved. Very recently, the area CA2 sub-region of the hippocampus, has aroused a great deal of interest, particularly in its major involvement in the processing of social memory. For the hippocampus to function properly, the balance between excitation and inhibition is essential. The area CA2 has the particularity of exhibiting a very high density of inhibitory parvalbumin (PV) interneurons which express unique properties. In patients and mouse models (Tg2576) of AD, dysfunction of PV interneurons leads to abnormal activity of the hippocampal neural network. Furthermore, this alteration of PV interneurons in the CA2 area is associated with the reduction of their extracellular matrix called perineuronal net (PNN). In this thesis, we hypothesized that PNNs around PV neurons are necessary for social memory and that their disappearance in the area CA2 is responsible for the social memory deficit observed in AD. Indeed, we show that the alteration of PNN around PV neurons in the area CA2 is sufficient to induce specific alterations in social memory in healthy mice. On the other hand, a specific improvement of social memory capacities is obtained in AD mice by stimulating the formation of PNNs in the area CA2. Finally, we report that Tg2576 mice exhibit an aberrant brain activity during a social task and this perturbation may be dependent on the disappearance of PNNs in the area CA2. Thus, our results reveal that the area CA2 of the hippocampus plays a major role in the social memory deficits associated with AD. Our work also identifies PV neurons and their extracellular matrix, the PNN, as crucial elements in the formation of social memory
Bauer, Virginie. "Contribution à l'influence des événements de vie dans l'étiologie des maladies démentielles de l'âgé". Thesis, Université de Lorraine, 2012. http://www.theses.fr/2012LORR0339/document.
Pełny tekst źródłaAmong the elderly, Alzheimer disease and related pathologies currently constitute a real public health issue. The anatomo-pathological lesions of these diseases may be clearly defined but their etiology remains uncertain and is likely multifactorial. As a clinician psychologist, theories involving psychism in the etiology of demential diseases among elderly, first held my attention. A review of the question enabled me to make a list supposed to be exhaustive and divided into 3 categories : psycho-dynamic, psycho-social theories and multifactorial integrative patterns. Among the latter, the one involving life events as risk factors motivated this double research. Thus is a qualitive procedure, 2 studies started in parallel. The first retrospective dealing with life stories of a population of 30 people affected by Alzheimer or related diseases, hosted in a protected life-unit ; the second prospective scanning through cognitive evolution based on several years for 30 elderly people unharmed by troubles at the start of the study (depending on their life stories having many or few life events). If a certain amount of disturbing events are recounted by relatives for most of the patients of the retrospective research, the prospective research shows that an important number of live events is neither a sufficient nor a necessary condition to represent a risk factor of cognitive troubles. On the other hand, the elaboration or non elaboration of there events, their traumatic or non traumatic aspect (linked with the received or not received support and help) seems to be determining in the cognitive evolution of the subjects. Finally, among most of the subjects for whom past events prove to be traumatic, a contemporary "loss"-like episode would revive memories and would be an accelerating factor of cognitive troubles and even a collapse to a memory pathology
Costa, Nadège. "Analyse médico-économique de différentes stratégies de prévention dans les maladies neurodégénératives : application à la maladie d’Alzheimer et à la maladie de Parkinson". Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10308.
Pełny tekst źródłaIn the current context of the growth of healthcare expenditures, health economics can help decision making in the process of resources allocation in the field of health. Neurodegenerative diseases (ND) are huge and costly diseases for which no cure is available to date. Prevention can be an axis of care of theses pathologies. It could help delay the disease progression or complications linked to these ones or to its treatments. In the frame of NDs, health economics can help to make choices in order to provide quality of healthcare to patients in the context of constraint resources. This thesis aimed to describe and analyze methodological characteristics of studies which assessed NDs costs, paying particular intention to informal costs. Our works revealed significant variations of methodological characteristics of a study to another. An additional effort must be performed by the scientific community in the field of methodological validation. This thesis also aimed to assess medical and economic consequences of prevention strategies in Alzheimer disease (AD) and Parkinson disease (PD). The observed results concerned the implementation of a directed prevention program in AD (I.e. multidomain intervention) and of a targeted prevention program in PD (i.e. therapeutic education). They confirmed the need to implement studies on prevention program on substantial time horizons
Deramecourt, Vincent. "Intérêt de l'analyse pluridisciplinaire dans la compréhension des mécanismes physiopathologiques des démences". Lille 2, 2009. http://tel.archives-ouvertes.fr/tel-00429256/fr/.
Pełny tekst źródłaMaleysson, Vincent. "Développement et caractérisation d'un nouveau modèle expérimental de la maladie d'Alzheimer chez le rat non transgénique". Thesis, Poitiers, 2016. http://www.theses.fr/2016POIT1401/document.
Pełny tekst źródłaAlzheimer's disease (AD) is characterized by a progressive decline in cognitive function with a memory impairment, a brain atrophy, and two histological hallmarks observed from post-mortem examination: extracellular β-amyloid plaques and intracellular tangles of the Tau protein abnormally phosphorylated. Numerous animal models of AD have been developed to understand and to test drugs against this pathology. However, any non-transgenic model of rodent developing amyloid plaques and the neurofibrilary pathology is currently available. The aim of this study is to develop the first non-transgenic model producing the two histopathological features of AD in the rat. The principle is to perform a concomitant intrahippocampal injection of a recombinant AAV (Adeno-Associated Virus) containing the human transgene tau with the P301L mutation, and of Aβ1-42 peptide, the main component of the amyloid plaques. After several experiments, we have obtained an animal model representative of the early steps of AD, i.e. with lesions focalized in one of the first affected brain structures in the AD: the hippocampus. The presence of the two histopathological hallmarks has been observed by immunohistofluorescence and associated with an astrogliosis. A memory impairment concerning more particulary the working memory, and abnormalities of the electrical activity of the brain and of the rapid eye movement sleep recorded by electroencephalography, are also characterized
Gay, Marion. "Conception, synthèse et évaluation de composes interagissant avec la dégradation des protéines pour le traitement de maladies neurodégénératives". Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S056.
Pełny tekst źródłaTwo physiopathological processes are involved in Alzheimer’s disease: the senile plaques (amyloid pathology) consisting of Aβ peptide aggregates and neurofibrillary tangles (Tau pathology) caused by the accumulation of hyper and abnormal phosphorylated Tau protein. Currently, only symptomatic treatments are available. Therefore, the development of curative drugs is a very active research field. Previous work in the laboratory led to the discovery of a family of compounds (MSBD) which lead-compounds are active on both pathologies of the Alzheimer’s disease. A drug candidate, AZP2006, emerged from that research and is currently in phase 1 clinical trials. Investigations on the identification of the biological target of AZP2006 led to p97/VCP protein, a target that has attracted considerable attention over the last few years for the treatment of neurodegenerative diseases (NDD).This PhD thesis deals with three main aspects:1) Study of the interactions between p97/VCP and developed compounds. STD-NMR studies have confirmed the interaction between AZP2006 and p97/VCP, though these preliminary results have to be confirmed by complementary techniques. AZP2006-based chemical probes were designed and synthesized to develop a FRET-based binding assay in order to get a more quantitative characterization of the binding.2) Development of new p97/VCP ligands. Based on previous ligands developed in the laboratory, a pharmacophore model was built. Subsequent, virtual screening and de novo design led to the identification of several chemical structures. Four families were synthesized and tested in vitro showing a good effect on Aβ peptides secretion and APP metabolism. These compounds are being tested on Tau hyperphosphorylation. The binding to p97/VCP was confirmed by STD-NMR.3) Development of multi target compounds acting on both the two pathology of Alzheimer disease and acetylcholinesterase (AChE). Activities of these compounds were validated in vitro (inhibition of AChE, Aβ peptides secretion, APP metabolism and Tau). In vivo, one of the compounds increased cognitive performance in two mice transgenic models.The results obtained during this PhD confirmed the therapeutic potential of p97/VCP in NDD and proposed new structures for their treatment
Lahmy, Valentine. "Validation préclinique de l'efficacité de l'ANAVEX2-73 dans des modèles transgénique et non transgénique de la maladie d'Alzheimer". Thesis, Montpellier 2, 2014. http://www.theses.fr/2014MON20084.
Pełny tekst źródłaAlzheimer's disease is the most common form of dementia in the elderly. There is however no efficient treatment to stop the disease progression. Tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmetanamine (ANAVEX2-73) is a mixed compound with moderate affinity for muscarinic and sigma-1 receptors. Preliminary data showed ANAVEX2-73 had anti-amnesic and neuroprotective poperties, in a non-transgenic model of Alzheimer's disease. The aim of this thesis is to improve knowledge about preclinical data of this molecule. We first showed that, in the non-transgenic AB(25-35) mouse model, ANAVEX2-73 prevented Tau protein hyperphosphorylation and AB(1-42) peptide seeding, two key parameters involved in Alzheimer's disease physiopathology. We also used this model tho show that ANAVEX2-73 prevented mitochondrial dysfunction, consistently reported as an early event of the disease in patients. The last part of this thesis showed that a two-month chronic treatment with ANAVEX2-73 in a transgenic mouse model of Alzheimer's disease reversed cognitive dysfunction and prevented loss of synaptic markers and increased of oxidative stress. However, we could not show a decrease of amyloid load in mouse brain after chronic treatment. Altogether, these results suggest that ANAVEX2-73 treatment could be effective to treat Alzheimer's disease. In addition to its neuroprotective and anti-amnesic property, it also prevents key hallmarks involved in the physiopathology of Alzheimer's disease
Héroux, Maryse. "Cerveau et thiamine, ses esters dans les maladies de Leigh et d'Alzheimer, son métabolisme et les récepteurs à glutamate dans l'encéphalopathie de Wernicke chez le rat". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1996. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq21472.pdf.
Pełny tekst źródłaPortet, Florence. "Troubles de la cognition dans la neurodégénérescence : intérêt prédictif des paramètres neuropsychologiques, fonctionnels, électrophysiologiques et génétiques : application à la SLA et à la maladie d'Alzheimer". Montpellier 1, 2003. http://www.theses.fr/2003MON1T028.
Pełny tekst źródłaSartori, Maxime Steno. "Etude in vivo de l'impact de la surexpression du gène BIN1 dans un modèle murin de la maladie d'Alzheimer". Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ131.
Pełny tekst źródłaLate Onset Alzheimer Disease represents more than 99% of total Alzheimer cases and it is not caused by genetic mutations. Among risk factors such as age, genetic compounds as BIN1 appear to be determinant for the pathological process establishment. This study aims to determine the BIN1 overexpression effect in mice and in a tauopathy context. In this study, BIN1 overexpression alone caused short term memory impairments linked with the cellular and molecular abnormalities. These disorders are exacerbated by a combination of TgBIN1 mice with a tauopathy model, both in males and females. Surprisingly, BIN1 overexpression rescued long term and spatial memory regarding the age and sex. Hippocampus appeared to be preserved from intracellular Tau inclusions. Moreover, fornix myelin is found intact. These elements highlighted BIN1 which is a key gene in tauopathie establishment. BIN1 neuroprotective activity is mediated by direct molecular interactions both with Tau and RTN4-A/Nogo-A
Casini, Elisa. "Le sommeil : une enjeu pour les couples confrontés aux maladies neuro dégénératives". Thesis, Lille 3, 2017. http://www.theses.fr/2017LIL30016/document.
Pełny tekst źródłaThis doctoral dissertation in sociology examines the sleep practices of ageing couples confronted with neuro-degenerative conditions. It aims to understand the time- and space-related aspects of these sleep practices, so central to couples’ lives, throughout the different stages of illness, and places particular emphasis on gender-based relations. Thirty couples were interviewed in their homes, 12 of whom were affected by Lewy Body Dementia and 18 by Alzheimer’s Disease. Empirical methods such as sleep journals, audio journals, and photographic documentation were incorporated into the study’s methodology. The study is divided into three branches. The first branch examines the role of “night-time guardian” assumed by the caregiving partner. The author was able to observe that a shift takes place from the status of sleeping partner to that of night-time caregiver. The role of the “night-time guardian” is characterized by domestic labor that takes the form of caregiving provided at night, a phenomenon the author calls “nocturnal domestic caregiving work”. The findings of the study show that this domestic night-time work can bring about a state of exhaustion in caregiving partners that can drive them to institutionalize the partner suffering from a medical condition. In addition to this domestic work, caregiving partners are prone to a state of night-time worry that results in a specific variety of sleep that can be described as “alert sleep”. This domestic work also goes largely unseen for two reasons: it is made up of activities that take place at night, and it often falls to women. The study's second branch offers an analysis of the impact of illness and cognitive disorders on the way areas of the home associated with sleep are organized, bringing to light the give-and-take that occurs where the marital bedroom is concerned. The author examined the reasons some sleep partners continue to insist on sleeping together. Also addressed are the bodily aspects of shared beds, a special context in which the bonds shared between bodies can be expressed in a unique way. The dissertation further explores the experience of placing distance between sleep partners: the meanings and practices surrounding the decision to sleep as a couple but in separate rooms. The final branch of the study examines a range of strategies used to manage sleep, such as taking sleeping medication, turning to in-home or institutional night-time caretaking, and day-time sleep. The author surveyed the reasons that caregiving partners accepted or refused to utilize these strategies, and the study’s findings show that the vulnerability represented by night and sleep can render it difficult to decide to use strategies to manage sleep
Burnouf, Sylvie. "Etude in vivo des relations entre la pathologie Tau et le système neurotrophique BDNF/TRKB". Lille 2, 2010. http://www.theses.fr/2010LIL2S026.
Pełny tekst źródłaMemory is the ability of our brain to encode, store and recall our experiences. It holds our personal history and is required for an appropriate interaction with the environment. Such events require a high level of plasticity in the hippocampus and the cortex. At the molecular level, neurotrophins are important modulators of structural and functional plasticity. Among them, Brain-Derived Neurotrophic Factor (BDNF) and its high-affinity receptor TrkB (Tropomyosine-related kinase B) are highly expressed in these cerebral regions, where beyond their role in trophic supply they can modulate synaptic transmission and synaptogenesis. Their role in memory processes has been shown in various studies. When memory is lost, as in Alzheimer’s disease (AD), people lose the ability to comprehend the world and as a result, they lose connections with themselves and with others. The main risk factor of AD being age, this neurodegenerative disease is becoming a major public health problem due to population ageing. AD patients brain exhibit two pathological hallmarks : extracellular amyloid deposits made of β-amyloid peptides (Aβ) and intraneuronal neurofibrillary tangles (NFT) made of aggregated hyper- and abnormally phosphorylated Tau proteins. In addition, BDNF/TrkB neurotrophic system has been shown to be impaired in AD patients’ cortex and hippocampus, suggesting a role in the disease physiopathology. In vivo studies using amyloid models of AD have pointed out a correlation between Aβ accumulation and BDNF decreased expression. However, whether Tau pathology impacts on BDNF/TrkB system signaling is unknown. Yet, in AD, Tau pathology follows a stereotyped and sequential pathway correlated with ognitive deficits. The lesions first appear in the hippocampal region, even before the first symptoms, and then reach the whole cortex at later stages. Therefore, in the laboratory we are most interested in Tau pathology, the mechanisms leading to its aggregation and the consequences on cellular physiology. We have developed the THY-Tau22 transgenic mouse model overexpressing a double-mutated human Tau transgene, which is under the control of a neuronal promoter. This model exhibits progressive learning and memory deficits, starting from the age of 3 months, in parallel to hippocampal Tau pathology, without major neuronal loss thereby mimicking early stages of AD. These characteristics make it a relevant model to study Tau pathology effects on hippocampal BDNF/TrkB system. Using biochemical techniques we have shown that BDNF/TrkB mRNA and protein levels were not decreased in THY-Tau22 mice hippocampus until the age of 12 months, suggesting no major influence of Tau pathology on BDNF/TrkB expression. However, electrophysiological experiments performed on hippocampal slices pointed out the fact that BDNF facilitating effects on synaptic transmission, known as synaptic facilitation, were abolished in hippocampal CA1 region of THYTau22 mice, as early as 3 months of age. This form of synaptic plasticity requires coupling of TrkB with NMDA glutamate receptor (NMDAR). In agreement with biochemical experiments showing a decreased expression of hippocampal NMDAR subunits, electrophysiological assessments on hippocampal slices uncovered impairment of NMDAR-mediated response. Overall, these data suggest that a form of BDNF-mediated synaptic plasticity is impaired in an early manner by Tau pathology, through functional alterations of NMDAR, thereby potentially contributing to memory alterations observed in AD. To further evaluate relationships between BDNF/TrkB signaling and Tau pathology, we investigated whether BDNF modulation had an impact on Tau pathology. Several studies suggest that physical activity prevents cognitive decline in AD. Yet, one major central effect of exercise is to induce a chronic increase of hippocampal BDNF. To study long-term effects of voluntary exercise on Tau pathology, 3 month-old THY-Tau22 mice and controls were given free access to a running wheel during 9 months. Our results show a decrease of Tau pathology in running THY-Tau22 mice hippocampus, together with prevention of spatial memory deficits and increase of hippocampal BDNF levels, suggesting beneficial effects of long-lasting modulation of BDNF/TrkB system on Tau pathology and its physiopathological consequences. Overall, results gathered during this thesis suggest a bilateral relationship between Tau pathology and BDNF/TrkB neurotrophic system, thereby highlighting the importance of neurotrophin modulation for AD treatment
Sitbon, Patrick. "La maladie d'Alzheimer". Paris 5, 1992. http://www.theses.fr/1992PA05P120.
Pełny tekst źródłaDagorne, Florence. "La maladie d'Alzheimer". Paris 5, 1990. http://www.theses.fr/1990PA05P004.
Pełny tekst źródłaGongoux-Trabelsi, Sophie. "La maladie d'Alzheimer". Paris 13, 2007. http://www.theses.fr/2007PA131030.
Pełny tekst źródłaAlzheimer’s Disease is a degenerative condition of the brain, predominantly affecting the memory, cognitive capacity and causingmotor skill disabilities affecting the patient’s daily life. The disease is associated with two types of cerebral damage : senile patches and neurofibrillaire degeneration. Age is the highest risk factor, which explains its predominance in the over 65s. In certain cases however, the disease presents in the under 65s, usually in those who have a genetic susceptability to it. In 2000, this disease affected 400,000 people in France, 8 million in Europe, and between 17 and 25 million worldwide, figures which are sure to rise. Today, over 860,000 people are affected in France and 26,6 million worldwide. The existing treatments, inhibitors of the cholinesterase (Aricept, Exelon et Réminyl) and the N-Methyl-D-Aspartate antogonists (Mémantine) are associated with reducting the cognitive decline but they are associated with reducting the cognitive decline. This is why the treatment research depends on molecules that are able to block the production of these lesions and therefore avoid the appearance and onset of the dementia. People suffering from this illness are taken care of by family members and health workers, whose aims are to help with daily life, stimulation by interaction and conversation, administer care, and most importantly, allow the sufferer to keep as much independence as possible within the constraints imposed upon them by their disease. The carer’s workload increases with the further development of the illness, leading to physical fatigue and considerable psychological stress, even more so if the carer is a family member, where the weight of responsibility is greater. They must search for information about the disease and its implications, follow healthcare professionnal’s advice, and ask for as much help as possible; from the healthcare system, but also from support groups, whose involvement proves invaluable to most. In effect, the carer of someone with Alzheimer’s Disease is synonymous with patience, devotion, emotional suffering, solitude, courage… and most of all, love
Horn, Jean-François. "Diagnostic des maladies neurodégénératives à partor d'images obtenues par tomographie d'émission monophotonique et à l'aide de méthodes de classement avec apprentissage supervisé". Paris 6, 2009. http://www.theses.fr/2009PA066454.
Pełny tekst źródłaVillez, Marion. "Le spécifique comme norme, l'invention comme pratique : l'accompagnement des personnes atteintes de maladie d'Alzheimer ou de maladie apparentée en établissement d'hébergement pour personnes âgées dépendantes". Thesis, Lille 3, 2015. http://www.theses.fr/2015LIL30042.
Pełny tekst źródłaThis research studies dementia care in nursing home, in France. It articulates three levels of analysis : a socio-historical investigation of public policies and professionals thinking about the importance given to dementia in nursing homes; an ethnographic field survey in a limited corpus of nursing homes; an extension to a macro-sociological level to put this reality back into its national context.Facing the dominant sector-wide approach based on an “adaptation to a target population” model, by observing the experience of the professionals and the managers’ choices, we discover a more complex reality, fostered by a global approach which attempting to combine two issues: the cohabitation of the whole community of residents and the provision of good care for all. Two mains ways seem to be opposed, in a context of constant debates and occultations of alternatives, the first one based on segregation of people with dementia (specific care in special unit that is widely accepted as standard), the second one opposing this segregation. Beyond that, care is built as a subtle dialectic based not only on an hybridization of different forms of care but also on the creation of new practices. Specific is the standard, creation is the practice. As a result, the place given to people with dementia and the social function of a care that account them, are ambivalent. The label assigned to them submit their life to institutional constraints. In the same time, they receive a privileged treatment, that professionals want to extend to all residents. Dementia care appears then as a social laboratory for changes, applies for each residents
Boutet, Claire. "Hippocampe et maladie d'Alzheimer". Paris 6, 2012. http://www.theses.fr/2012PA066151.
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