La maladie d’Alzheimer est une maladie très complexe, aujourd’hui encore mal comprise et cette démence est devenue un réel problème de santé publique. La protéine précurseur de l’amyloïde (APP) et la protéine Tau sont deux acteurs majeurs impliqués dans la maladie. De nombreuses recherches se sont investies dans la compréhension du métabolisme, de l’action et de l’implication de ces deux protéines dans les mécanismes pathologiques de la maladie et d’autres maladies neurodégénératives. Elles sont notamment l’objet de la plupart des approches thérapeutiques passées et actuelles, et étudiées pour le diagnostic biologique de la maladie. Dans ce projet de thèse, notre objectif fut d’explorer le métabolisme des protéines APP et Tau au cours de la différenciation neuronale à l’aide d’outils biochimiques et de systèmes innovants d’immunodétection multiplex très sensibles (MSD®) dans plusieurs modèles de culture cellulaire de la maladie. L’objectif était d’obtenir une vision globale des processus physiopathologiques au travers d’analyses d’échantillons générés au cours de la différenciation neuronale de cellules souches pluripotentes induites (iPSC) de patients Alzheimer comparées aux cellules souches embryonnaires humaines (hESC). Nous avons ainsi généré et caractérisé plusieurs lignées cellulaires d’IPSC d’une personne saine contrôle et de patients atteints des formes sporadiques et familiales de la maladie. Ce projet offre l’opportunité unique de combiner des approches innovantes pour tenter de comprendre comment les fragments et les peptides Ab sont générés, ainsi que les modifications de Tau en conditions normales et pathologiques. / Amyloid precursor protein (APP) and Tau protein are two main molecular actors of the Alzheimer’s disease (AD), which is of prime importance in Human Health. Intensive research is ongoing to understand these proteins’ metabolism, action and implication in the pathological mechanism of these affections. They are the target of most therapeutic approaches and are used for biological diagnosis. In the present PhD project, our objective was to investigate neuronal APP and Tau protein processing and metabolism using biochemical tools and innovative multiplex immunodetection system (MSD®) in diverse cell culture models of AD. The goal was to get a comprehensive view oh physiopathological processes based on the analysis of samples generated in neuronal differentiated human embryonic stem cell and induced pluripotent stem cells derived from AD-patients. We generated several cell lines from an healthy control individual, and AD patients showing sporadic and familial forms of the disease. This project offer the unique opportunity to combine state-to-the-art approaches to understand how the APP fragments and peptides are generated as well as the modifications of the Tau protein in normal and pathological situation.

La fibrillation anormale de la protéine tau est un phénomène présent dans de nombreuses maladies neurodégénératives, dont la maladie d’Alzheimer, et conduit à la formation de fibres amyloïdes appelées dégénérescences neurofibrillaires. L’utilisation de molécules organiques capables de marquer ces fibres ou d’inhiber leur formation revêt un intérêt à la fois diagnostic et thérapeutique dans la maladie d’Alzheimer. Une série d’aurones a été synthétisée et leur capacité à interagir et interférer avec le processus de fibrillation a été évaluée in vitro sur des modèles de fibres de tau développés ou optimisés lors de ce projet. Ce travail a permis de montrer que des aurones polyhydroxylées sont capables d’agir comme sonde et/ou comme inhibiteur du processus de fibrillation. Afin d’élargir les applications possibles des aurones, la ligation d’aurones avec des biomolécules ou encore leur radiomarquage a également été évaluée. / The fibrillation of the tau protein occurs in many neurodegenerative diseases, including Alzheimer’s disease, and leads to the formation of amyloid fibres called neurofibrillary tangles. Using organic molecules able to mark these fibres or inhibit their formation provides an interest both in diagnosis and therapy in Alzheimer’s disease. A series of aurones was synthesized and their ability to interfere with the fibrillation process was evaluated in vitro on models of tau fibres developed in this project. This work shows that polyhydroxylated aurones are able to act both as probes and as inhibitors of the fibrillation process. The ligation of these aurones with biomolecules or their radiolabelling has also been investigated.

[pt] A doença de Alzheimer é uma patologia multifatorial que, nos dias atuais, re-presenta a forma mais conhecida de demência em idosos. Baseado na hipótese me-tálica, pesquisas demonstraram que a interação de certos íons metálicos endógenos, como o Fe3+ e o Cu2+, com o peptídeo A beta provoca uma aceleração da formação de espécies oligoméricas e ainda contribui para o aumento do estresse oxidativo. Neste ínterim, a proposição de MPACs (do inglês, Metal-Protein Attenuating Coum-pounds, compostos atenuadores da interação metal-proteína) é uma abordagem pro-missora para evitar o progresso da demência, pois estas moléculas apresentam afi-nidade moderada por íons metálicos. Neste trabalho, sintetizaram-se três potencias MPACs hidrazônicos, INHOVA, 2PCAFUR e FUROVA e um complexo inédito de vanádio(IV), [VO(INHOVA)2(OH2)]·2HCl 1/2 MeOH (1), proposto como mo-delo de veículo para esses compostos. A caracterização destas moléculas foi possí-vel a partir de diferentes técnicas, como espectroscopia vibracional na região do infravermelho (IV), análise elementar (CHN), ressonância magnética nuclear de 1H (RMN de 1H), difração de raios-X em monocristal, ressonância paramagnética ele-trônica (EPR) e análise termogravimétrica (TGA). Os ligantes hidrazônicos não co-ordenados são suscetíveis à hidrólise, conforme estudado por espectroscopia de ab-sorção no UV-Vis. O complexo de vanádio (1), por outro lado, apresenta maior estabilidade, podendo atuar como veículo para esses e outros MPACs, preservando a integridade do ligante em solução. Neste contexto, complexos metálicos de vanádio tendo como ligantes INHOVA, 2PCAFUR e FUROVA se apresentam como bons candidatos a estudos mais aprofundados, a fim de avaliar sua viabilidade como possíveis carreadores de MPACs no tratamento da doença de Alzheimer. / [en] Alzheimer s disease is a multifactorial pathology that, currently, represents the most known form of dementia in the elderly. Based on the metal hypothesis, studies have shown that the interaction of certain endogenous metal ions, such as Fe3 plus and Cu2 plus, with the A beta peptide accelerates the formation of oligomeric species and also contributes to the increase of oxidative stress. In this context, the proposition of MPACs (Metal-Protein Attenuating Compounds) is a promising approach to prevent the progression of dementia because these molecules exhibit moderate affinity for metal ions. In this work, three potential hydrazonic MPACs were syn-thesized, INHOVA, 2PCAFUR and FUROVA and a novel vanadium(IV) complex, [VO(INHOVA)2(OH2)] 2HCl.1/2MeOH (1), proposed as vehicle model for these compounds. The characterization of these molecules was possible from different techniques such as vibrational spectroscopy in the infrared (IR) region, elemental analysis (CHN), proton nuclear magnetic resonance (1H-NMR), X-ray diffraction in monocristal, electronic paramagnetic resonance (EPR) and thermogravimetric analysis (TGA). Uncoordinated hydrazonic ligands are susceptible to hydrolysis as studied by UV-Vis absorption spectroscopy. The vanadium complex (1), on the other hand, present greater stability, being able to act as vehicle for this and other MPACs, preserving their integrity in solution. In this context, vanadium metal com-plexes containing INHOVA, 2PCAFUR and FUROVA as ligands present them-selves as good candidates for further studies in order to evaluate their viability as possible drugs for the treatment of Alzheimer s disease.

Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2012-10-16T07:17:36Z (GMT). No. of bitstreams: 0Bitstream added on 2013-07-16T17:22:43Z : No. of bitstreams: 1 101753.pdf: 3051234 bytes, checksum: 49cb8f57b24dcfa2cb44eb84d0a5751e (MD5)

Le vieillissement de la population des tunisiens des Trente Glorieuses en France, n’est pas épargné par le phénomène Alzheimer, à l’heure où la maladie connaît une stigmatisation et une popularisation intenses tant dans les sociétés occidentales que dans les pays en voie de développement. En référence aux travaux de M. Péruchon, G. Le Gouès ou encore A.-M. Gardey, la mise en évidence de l’involution démentielle, accompagnée de l’atteinte des repères et des limites identitaires, sont abordées selon une approche transculturelle. L’analyse du fonctionnement psychique de dix tunisiens vivant en France en comparaison avec dix tunisiens vivant en Tunisie, tous âgés de plus de soixante ans et souffrant de la démence dite Alzheimer, est proposée à partir de protocoles issus du Thematic Apperception Test. Tandis que l’évidement représentationnel ne diffère pas d’une population à l’autre, l’étude a mis en évidence une altération de la représentation de soi plus marquée dans le groupe de sujets immigrés. L’épreuve migratoire semblerait également renforcer la recherche d’une relation d’objet archaïque où les pulsions d’attachement et d’agrippement tiennent une place centrale. Entre voyage et décolonisation, la double culture est ici présentée par un travail qui plaide en faveur d’un relativisme des données universelles véhiculées par le monde biomédical. Comprendre les représentations culturelles en présence, vise à nous fournir des éléments pour une prise en charge adaptée de nos aînés ; accablés par les effets de l’appartenance à une catégorie socio-culturelle minoritaire, et dont l’identité est souvent définie par la perte et le déficit neuro-dégénératif / The aging of the Tunisian population during the so called TrenteGlorieuses in France is not spared by Alzheimer phenomenon at a time when the disease has an intense stigma and popularization as much in western societies as in developing countries . With reference to the work of M. Peruchon, G. Le Gouès or A.-M. Gardey highlight of the dementia involution in addition to the achievement of benchmarks and identity limits are all addressed in a transcultural approach. The analysis of psychic functioning of ten Tunisians living in France compared with ten Tunisians living in Tunisia, all over the age of sixty years and suffering from the dementia so called Alzheimer's is suggested with protocols coming from the Thematic Apperception Test. While the representational ‘scooping out’ does not differ from one population to another, the study has highlighted a modification of a self-representation more pronounced in the group of immigrant subjects. The migration phase seems also to strengthen the research of archaic object relationship where the impulses of attachment and grasping have an important role. In between travel and colonization, the joint-culture is presented here in a job that speaks in favour of a relativism of universal data carried out by the biomedical world. Understand cultural representations so mentioned aims to provide us with elements for an appropriate care of our seniors overwhelmed by the effects of belonging to a socio-cultural minority whose identity is often defined by the loss and neurodegenerative deficit.

A leitura em hipertexto foi difundida por meio da tecnologia da informação, sendo importante identificar em quais áreas esta tecnologia melhora a compreensão textual, quando comparada ao texto linear. Com o objetivo de verificar se o hipertexto facilita o reconto de idosos com Demência de Alzheimer, analisou-se 40 idosos: 25 com DAs prováveis, sendo 12 leves e 13 moderados; e 15 sem demência, com idades entre 60 e 84 anos e escolaridade acima de 4 anos. A compreensão textual mostrou ser uma tarefa sensível aos participantes com demência, cujo desempenho foi significativamente pior do que o dos idosos normais. A história em hipertexto auxiliou os participantes com DA leve. Os grupos de DA leve e moderada lembraram da idéia principal da história, contudo somente o grupo de demência inicial lembrou de detalhes. Verificou-se que quanto mais grave a demência maior o número de acréscimos ao enredo e menor o percentual de proposições lembradas. Os resultados sugerem que, devido à dificuldade das memórias de trabalho e episódica, os participantes recorreram a recursos, ainda presentes, da memória semântica para completar a história. / Hypertext reading was disseminated by means of information technology, and it is important to identify the areas in which this technology improves textual comprehension in comparison to linear text. With the objective of determining if hypertext makes recounting easier for elderly people with Alzheimer’s Dementia (AD), 40 elderly people, from 60 to 84 year of age and at least 4 years of schooling, were studied: 25 with probable AD, 12 of which mild and 13 moderate, and 15 that do not present dementia. Textual comprehension proved to be an arduous task for the participants with dementia, whose performance was significantly worse than normal elderly people. The story in hypertext helped the participants with mild AD. The groups with mild to moderate AD were able to remember the main idea of the story, though only the group with initial dementia remembered the details. It was established that the more serious the dementia, the greater the number of facts added to the plot and the lesser the percentage of propositions remembered. The results suggest that due to difficulties with the working memory, the participants appealed to resources still available in the semantic memory to complete the story.

Made available in DSpace on 2015-07-22T20:49:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-27 / Objetivos: avaliar as praxias verbal e não-verbal em pacientes com doença de Alzheimer (DA) e identificar os erros práxicos verbais em diferentes fases da doença, além de verificar a similaridade entre as suas ocorrências. Métodos: foram avaliados 90 indivíduos, 30 em cada fase da DA (leve, moderada e grave), submetidos às escalas: Escala clínica da demência (CDR), Mini-exame do estado mental (MEM) e avaliação das atividades instrumentais de vida diária de Lawton, além da avaliação das praxias, por meio das tarefas de agilidade oral do teste de Boston, para a comparação com os dados de normalidade, e do Protocolo de Avaliação da Apraxia Verbal e Não-verbal, para a comparação do desempenho entre os três grupos. Resultados: Em relação à população estudada, 66 pacientes eram mulheres, a média da idade foi de 80,2 ±7,2 e da escolaridade de 4,2 ±3,5 anos. As médias de agilidade oral (verbal e não-verbal) dos grupos estudados foram significativamente menores do que as da população normal. As alterações práxicas verbais e não-verbais aumentaram com a progressão da doença. Quanto aos tipos de erros, os erros de omissão e substituição apresentaram maiores médias, seguidos de ensaio, repetição, autocorreção e adição. O erro do tipo adição determinou padrões de erros diferentes entre as fases da doença. Conclusões: os pacientes com DA apresentaram apraxia verbal e não-verbal que aumentaram com a gravidade demência. / Purpose: to assess the speech and orofacial apraxia in Alzheimer’s disease (AD) and identify praxic speech errors at different stages of the disease and to verify the similarity among their occurrences. Methods: thirty subjects in each stage of AD (mild, moderate and severe) were submitted to the following assessment: Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE) and Lawton Instrumental Activities of Daily Living, and praxis tasks, using the oral agility subtest of the Boston diagnostic aphasia examination and the protocol assessment speech and orofacial apraxias. Results: there were 66 women, the mean age was 80,2±7,2 years and means educational was 4,2 ±3,5 years. The means in the oral agility task of AD patients were significantly lower than of the normal population. Difficulties in verbal and nonverbal praxis increased with the progression of the disease. Regarding the types of errors, omission and substitution were more common, followed by trial-and-error, repetition, self-correction and addition. The error type addition determined different patterns of errors between stages of the disease. Conclusions: the speech and orofacial praxias of patients with AD were impaired and deteriorated according to the stage of the disease. / TEDE / BV UNIFESP: Teses e dissertações

La maladie d'Alzheimer est une pathologie neurodégénérative caractérisée par une perte progressive des fonctions cognitives. Cette perte des fonctions cognitives est directement liée à une atteinte neuronale et plus particulièrement synaptique. Deux caractéristiques histopathologiques en lien avec des dérégulations protéiques sont retrouvées chez les patients atteints de la MA : les plaques séniles extracellulaires composées de peptides β-amyloïdes (Aβ) fibrillaires et la dégénérescence neurofibrillaire constituée d'agrégats intracellulaires de protéines tau hyper et anormalement phosphorylées. Les formes agrégées de ces protéines ont longtemps été considérées comme neurotoxiques, cependant, il est maintenant avéré que les formes solubles de ces protéines dérégulées étaient à l'origine de la pathologie. Les synapses excitatrices situées au niveau des épines dendritiques sont les cibles du peptide Aβ sous forme soluble et oligomèrique (Aβo). Ce dernier en altère la fonction et induit leurs pertes. Récemment, il a été montré que cette action synaptotoxique de l'Aβo est dépendante de la protéine tau. De plus, dans un autre modèle de tauopathie, la démence fronto-temporale avec syndrome parkinsonien liée au chromosome 17 (FTDP-17), la synaptotoxicité de tau s'est révélée dépendante de son état de phosphorylation. Ainsi, il émerge le concept de tau synaptique dans un contexte pathologique. Cependant, des études plus récentes ont montré que, en condition physiologique, une petite portion de tau se retrouve au niveau de la synapse. Au regard de ces nouvelles données, il est possible que tau, en plus d'être une protéine axonale, nucléaire et membranaire, soit aussi synaptique. Dans ce contexte, les travaux présentés dans cette thèse visent à étudier l'implication de la protéine tau dans la fonction synaptique et les perturbations induites par la présence d'Aβo. Ces travaux ont été effectués sur un modèle cellulaire de cultures primaires de neurones corticaux et sur tranche d'hippocampe de souris par des méthodes biochimiques et d'analyse dynamique en microscopie confocale sur cellules vivantes. Afin d'étudier l'impact d'une activation synaptique sur un système de culture neuronal, l'utilisation combinée de la bicuculline, antagoniste des récepteurs gabaergique GABAa et de 4-amino pyridine, bloqueur de canaux potassique, permet d'établir une potentialisation à long terme sur les synapses. Grâce à un protocole d'extraction permettant d'isoler le compartiment post-synaptique (fraction contenant la densité post synaptique dont le marqueur protéique PSD-95), nous avons montré que l'activation synaptique enrichit la fraction PSD en protéine tau suggérant son implication dans les phénomènes de plasticité synaptique. L'étude du cytosquelette d'actine prépondérant au niveau synaptique a révélé que l'actine filamenteuse est un partenaire de tau. Dans un contexte pathologique, l'incubation d'Aβo induit le recrutement de tau à la synapse et perturbe l'organisation du cytosquelette d'actine. Ce changement structurel du cytosquelette d'actine pourrait être à l'origine des perturbations de la plasticité et du maintien synaptique induit par Aβo. En conclusion, l'ensemble des résultats de cette thèse suggère que tau exerce une fonction physiologique au sein de la synapse impliquant une interaction avec le cytosquelette d'actine et qu'en conditions pathologiques (induites par Aβo), on observe une altération fonctionnelle du rôle de tau à la synapse qui pourrait participer aux perturbations cognitives caractéristiques de la MA. / Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive loss of cognitive functions. This loss of cognitive functions is directly related to neuronal impairment, and more specifically, synaptic dysfunction. Two histopathological features found in AD patients' brains are related to protein deregulation: extracellular neuritic plaques composed of fibrillar β-amyloid peptide (Aβ) and intracellular aggregates composed of hyper-phosphorylated tau, named neurofibrillary tangles. Aggregated forms of these peptides have been considered neurotoxic, however, it is now recognized that soluble forms of these deregulated proteins are causal to the pathology. Soluble, oligomeric forms of Aβ peptide (Aβo) target excitatory synapses where they diminish synaptic function and cause loss of dendritic spines. Recently, it has been shown that the Aβo synaptotoxicity is tau-dependent. Another tauopathy, fronto-temporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), exhibits synaptotoxicity, which has proved to be dependent on the phosphorylation state of tau. Thus, emerged the concept of synaptic tau in a pathological context. Recent studies have shown that a small quantity of tau is present in synapses under physiological conditions. These new data suggest that tau is a synaptic protein, in addition to being axonal, nuclear and membrane-associated. In this context, the work presented in this thesis characterizes the involvement of tau in synaptic function and its Aβo-induced disturbances. This work was conducted using primary cortical neurons cultured from mice and hippocampus slices and employed biochemical methods and confocal live-cell imaging. To study the impact of a synaptic activation on synaptic tau, we combined bicuculline, an antagonist of GABAa receptors and 4-amino-pyridine, potassium channel blocker, to establish long-term synaptic potentiation. By isolating the post-synaptic compartment (i.e. the fraction containing the post synaptic density and its marker PSD-95), we have shown that synaptic activation induced an enrichment of tau in PSD. This suggests its involvement in synaptic plasticity. The study of the actin cytoskeleton, which is specifically enriched in dendritic spines, revealed that filamentous actin is a molecular partner of tau, which may provide a means of recruiting tau to the synapse. Turning our attention to a pathological context, exposure to Aβo induced tau recruitment to the synapse and disrupts the actin cytoskeleton organization without exogenous synaptic stimulation. This structural modification of the actin cytoskeleton could underlie the disturbance of plasticity and synaptic maintenance induced by Aβo. In conclusion, this thesis provides evidence that tau performs a physiological synaptic function that involves an interaction with the actin cytoskeleton. Further, the synaptic function of tau is altered in pathological conditions (i.e. exposure to Aβo), and may contribute to the cognitive disturbances in AD.

A atividade física (AF) demonstrou um efeito protetor contra a doença de Alzheimer (DA), mas não se sabe qual a influência da AF sobre o biomarcador de neuroproteção, a glicogênio sintase-quinase 3 (GSK3). O Objetivo do nosso estudo é avaliar o efeito do exercício físico sobre os níveis séricos da GSK3. Foi realizado um estudo observacional de corte transversal, no qual 72 idosos saudáveis e sem demência foram selecionados e divido em dois grupos de acordo com o nível de atividade física. A atividade da GSK3 foi semelhante entre os grupos estudados, houve uma tendência a maior inativação da GSK3 (fator neuroprotetor) entre os ativos e maior ativação entre os sedentários e muito ativos, porém sem significância estatística. É possível que a atividade física de baixa intensidade já tenha um efeito protetor. Uma maior população de idosos e métodos mais precisos de mensurar AF serão necessários para demonstrar efeito da AF sobre a GSK3 / The physical activity (PA) was demonstrated to have a protective effect against Alzheimers disease, but the influence of exercising on the biomarker of neuroprotection such as Glycogen synthase kinase 3 (GSK-3) are hitherto imprecise. This study aims at assessing the effect of PA on the serum levels of GSK3. We have performed a cross-sectional observational study with 72 healthy elders, without dementia, selected and classified into two groups according to the level of PA. The GSK3 activity resulted similar in both groups; there was a tendency of inactivation of GSK3 (neuroprotective factor) among active elders and a higher activation among sedentary and highly active elders, although without statistical significance. Its possible that low-intensity physical activity may already have a protective effect. Further studies with higher number of participants and methods more accurate to measure PA will be needed to demonstrate effect of PA on the GSK3

Made available in DSpace on 2016-06-02T19:48:19Z (GMT). No. of bitstreams: 1 4177.pdf: 5761817 bytes, checksum: cb8d207716a1afe86708253767f3f7ee (MD5) Previous issue date: 2012-02-24 / Financiadora de Estudos e Projetos / Alzheimer's disease (AD) is the most common cause of dementia in people over 65 years. Platelet studies with ADAM10 have shown to decrease its expression in AD patients. The association between cognitive testing and molecular biomarkers such as levels of platelet ADAM10 protein can be important tools for the accurate and early diagnosis of AD. The aim of this research was to investigate the relationship between the Mini-Mental State Examination - MMSE and the Clinical Dementia Rating - CDR with the ADAM10 expression in two groups of elderly. 30 subjects with AD were compared with 25 matched controls by sex, age and education. All ethical considerations were observed. Individual evaluations were carried out and applied the CDR and MMSE, and then performed the collection of biological material of the elderly. The techniques SDS-PAGE and Western blotting were used to quantify the ADAM10 content in platelets. After collecting the data, they were analyzed using statistical methods of comparison, correlation, association, logistic regression and diagnostic accuracy. The results show that the ratio ADAM10/_-actin was reduced in elderly patients with AD and that this reduction is intensified with the progression of the disease. MMSE and CDR have significant correlations with the values of ratio ADAM10/_-actin, this being the only statistically significant variable (p = 0.01) to increase the probability of occurrence of AD. The cutoff value < 0.4212 in ROC curve captures 70% sensitivity and specificity of 80.77% for the presence of AD according to the ratio ADAM10/_-actin. Therefore, the ratio ADAM10/_-actin seems to be a relevant biomarker for AD. The results bring important contributions to an accurate diagnosis of Alzheimer's disease from the perspective of ADAM10 as a biomarker for this disease. The results are preliminary but encouraging. / A doença de Alzheimer (DA) é a causa mais comum de demência em pessoas com mais de 65 anos de idade. Estudos plaquetários com a ADAM10 têm demonstrado diminuição na sua expressão em pacientes com DA. A associação entre testes de avaliação cognitiva e biomarcadores moleculares, tais como os níveis plaquetários da proteína ADAM10 podem contribuir para o diagnóstico preciso e precoce da DA. O objetivo desta pesquisa foi verificar a relação entre o Mini-Exame do Estado Mental MEEM e o Clinical Dementia Rating CDR com a expressão da ADAM10 em dois grupos de idosos. 30 sujeitos com DA foram comparados com 25 controles, pareados segundo sexo, idade e escolaridade. Todos os cuidados éticos foram observados. Foram realizadas avaliações individuais e aplicados o CDR e MEEM e em seguida realizada a coleta do material biológico dos idosos. As técnicas SDSPAGE e Western Blotting foram utilizadas para detecção da ADAM10. Após a coleta dos dados, estes foram analisados por meio de métodos estatísticos de comparação, correlação, associação, regressão logística e acurácia diagnóstica. Os resultados mostram que a razão ADAM10/_-actina apresenta-se diminuída em idosos com DA e que esta redução se intensifica com o avanço da doença. O MEEM e o CDR apresentam correlações significativas com os valores da razão ADAM10/_-actina, sendo esta a única variável estatisticamente significativa (p = 0,01) para o aumento da probabilidade de ocorrência da DA. O ponto de corte < 0,4212 da curva ROC capta sensibilidade de 70% e especificidade de 80,77%, para a presença de DA segundo a razão ADAM10/_-actina. Portanto, a razão ADAM10/_-actina parece ser um relevante biomarcador para DA. Os resultados trazem contribuições importantes para um diagnóstico preciso da doença de Alzheimer na perspectiva da ADAM10 como um biomarcador para esta doença. Os resultados são preliminares, porém animadores.