Maladie d'Alzheimer : Etude des marqueurs pathologiques dans le cortex frontal humain et corrélations anatomo-cliniques

La maladie d'Alzheimer (MA), forme de démence la plus fréquente, est caractérisée précocement par des troubles de la mémoire, puis par une détérioration cognitive progressive, corrélée avec la progression des lésions cérébrales que sont les dépôts de protéine ß-amyloïde, notamment dans les plaques séniles, et la dégénérescence neurofibrillaire qui touche en priorité les grands neurones pyramidaux de l'hippocampe et du cortex cérébral. La perte ou les dommages synaptiques sont aussi prépondérants et conduisent à la mort neuronale et à la perte de réseaux fonctionnels notamment au niveau des protéines présynaptiques comme la synaptophysine et postsynaptiques comme PSD-95 (Leuba et al. 2008), ainsi que des récepteurs NMDA (NMDAR) liés à PSD-95 et jouant un rôle prédominant dans le fonctionnement synaptique. Notre étude s'est portée une des régions du cortex frontal correspondant à l'aire de Brodmann 10, encore peu étudiée dans la littérature scientifique, qui peut être touchée de manière plus ou moins importante dans la MA, entraînant des troubles de l'humeur et du comportement ainsi que des répercussions sur les fonctions exécutives. L'étude a pour but d'identifier et de quantifier les dépôts de protéine ß-amyloïde et les lésions neurofibrillaires ainsi que les changements de protéines synaptiques et de récepteurs NMDA dans cette région entre une population contrôle et AD, et de la comparer avec d'autres régions déjà partiellement étudiées dans le laboratoire, notamment l'aire 9 qui lui est adjacente et les aires cingulaires 24 et 25. L'analyse est faite de manière qualitative et semi-quantitative au microscope optique sur des coupes colorées avec des méthodes immunohistochimiques. De possibles corrélations anatomo-cliniques sont recherchées dans les cas AD. La région FC10 est touchée par la MA avec une présence de plaques séniles et de dégénérescences neurofibrillaires plus marquées chez les cas atteints de la MA ce qui n'est pas le cas des protéines synaptiques. Le comportement des deux marqueurs pathologiques dans FC10 est comparable aux autres régions cérébrales étudiées notamment à la région adjacente, FC9, contrairement aux marqueurs synaptiques qui selon la région ont un comportement plus variable. L'effet de l'âge dans l'évolution de la physiopathologie de la MA pour les marqueurs pathologiques a été mis en évidence dans la région FC10. Les régions EC et FC9 n'ont pas montré de microhémorragie synonyme d'une possible contribution vasculaire. L'étude de cette région a permis de mettre en évidence l'implication de FC10 dans la MA. Elle montre des points communs avec les autres régions cérébrales notamment vis-à-vis des plaques séniles et des DNF.

Anàlisi del coneixement, de l'actitud i de l'ús que fan els cuidadors informals dels malalts d' Alzheimer en el domicili, de les contencions mecàniques i farmacològiques

L’objectiu d’aquest estudi consisteix en saber quins coneixements posseeixen, quines actituds i quin ús fan els cuidadors informals de persones diagnosticades d’Alzheimer en el domicili, de les contencions mecàniques i farmacològiques. Aquest projecte es tracta d’un disseny exploratori, descriptiu i transversal. Per a realitzar-lo es prendrà com a mostra a cuidadors principals informals, que tinguin al seu càrrec persones diagnosticades d’Alzheimer que siguin usuàries de l’atenció primària dels serveis sanitaris públics, de la província de Barcelona. L’estudi integrarà dues fases: la primera consistirà en realitzar una prova pilot a un nombre reduït de persones que servirà per avaluar i perfeccionar l’eina de la recollida de dades (els instruments a emprar seran una enquesta d’elaboració pròpia i entrevistes) i la segona consistirà en efectuar la recollida de dades a partir de l’enquesta modificada i validada en la fase anterior. En la fase pilot es realitzarà l’anàlisi de les dades a través de la tècnica coneguda com <del contingut>> i en la fase següent, s’utilitzarà el paquet estadístic SPSS versió 21.0.0.

Un programa psicosocial: programa psicoestimulatiu integral (P.P.I.) amb persones afectades de malaltia d' Alzheimer

L'any 2011 la malaltia d'Alzheimer es situava com la quarta causa de mort més freqüent amb un augment de fins a 11.907, més del doble de morts que l'any 2000 (INE). Aquestes dades demostren l'augment del número de persones que pateixen una demència a mesura que envelleixen i una de les explicacions és l'augment de l'esperança de vida. Per aquest motiu l'estudi de la qualitat de vida ha adquirit una gran importància des de la dècada dels 90. La qualitat de vida és un concepte especialment subjectiu pel fet que cada persona la viu segons la pròpia percepció de salut i benestar i el grau d'adaptació a l'entorn que l'envolta. Per aquest motiu es planteja un programa de psicoestimulació integral (PPI) centrat en les individualitats de cada persona: valors, interessos, història ocupacional..., des de la filosofia de la Teràpia Ocupacional. El projecte està elaborat mitjançant la metodologia qualitativa utilitzant l'enquesta en profunditat semi-estructurada per a realitzar les entrevistes i obtenir la informació principal a l'inici i al final del programa juntament amb tota la informació que s'obtingui de l'observació participant del dia a dia de cada un dels professionals per tal d'estudiar fins a quin punt aquesta atenció centrada en la persona contribueix a millorar la qualitat de vida de les persones afectades de Malaltia d'Alzheimer que reben tractaments no farmacològics com el proposat en aquest projecte. Com a tot estudi es poden trobar alguns factors condicionants com pot ser l'evolució pròpia de la malaltia amb les conseqüències negatives que això comporta i/o el número de participants que formen la mostra.

On the Selection of Non-Invasive Methods Based on Speech Analysis Oriented to Automatic Alzheimer Disease Diagnosis

The work presented here is part of a larger study to identify novel technologies and biomarkers for early Alzheimer disease (AD) detection and it focuses on evaluating the suitability of a new approach for early AD diagnosis by non-invasive methods. The purpose is to examine in a pilot study the potential of applying intelligent algorithms to speech features obtained from suspected patients in order to contribute to the improvement of diagnosis of AD and its degree of severity. In this sense, Artificial Neural Networks (ANN) have been used for the automatic classification of the two classes (AD and control subjects). Two human issues have been analyzed for feature selection: Spontaneous Speech and Emotional Response. Not only linear features but also non-linear ones, such as Fractal Dimension, have been explored. The approach is non invasive, low cost and without any side effects. Obtained experimental results were very satisfactory and promising for early diagnosis and classification of AD patients.

On Automatic Diagnosis of Alzheimer's Disease based on Spontaneous Speech Analysis and Emotional Temperature

Alzheimer's disease is the most prevalent form of progressive degenerative dementia; it has a high socio-economic impact in Western countries. Therefore it is one of the most active research areas today. Alzheimer's is sometimes diagnosed by excluding other dementias, and definitive confirmation is only obtained through a post-mortem study of the brain tissue of the patient. The work presented here is part of a larger study that aims to identify novel technologies and biomarkers for early Alzheimer's disease detection, and it focuses on evaluating the suitability of a new approach for early diagnosis of Alzheimer’s disease by non-invasive methods. The purpose is to examine, in a pilot study, the potential of applying Machine Learning algorithms to speech features obtained from suspected Alzheimer sufferers in order help diagnose this disease and determine its degree of severity. Two human capabilities relevant in communication have been analyzed for feature selection: Spontaneous Speech and Emotional Response. The experimental results obtained were very satisfactory and promising for the early diagnosis and classification of Alzheimer’s disease patients.

Investigation of ICA algorithms for feature extraction of EEG signals in discrimination of Alzheimer disease

In this paper we present a quantitative comparisons of different independent component analysis (ICA) algorithms in order to investigate their potential use in preprocessing (such as noise reduction and feature extraction) the electroencephalogram (EEG) data for early detection of Alzhemier disease (AD) or discrimination between AD (or mild cognitive impairment, MCI) and age-match control subjects.

Alzheimer disease diagnosis based on automatic spontaneous speech analysis

Alzheimer’s disease (AD) is the most prevalent form of progressive degenerative dementia and it has a high socio-economic impact in Western countries, therefore is one of the most active research areas today. Its diagnosis is sometimes made by excluding other dementias, and definitive confirmation must be done trough a post-mortem study of the brain tissue of the patient. The purpose of this paper is to contribute to im-provement of early diagnosis of AD and its degree of severity, from an automatic analysis performed by non-invasive intelligent methods. The methods selected in this case are Automatic Spontaneous Speech Analysis (ASSA) and Emotional Temperature (ET), that have the great advantage of being non invasive, low cost and without any side effects.

Postsynaptic density protein PSD-95 expression in Alzheimer's disease and okadaic acid induced neuritic retraction.

In order to understand how plasticity is related to neurodegeneration, we studied synaptic proteins with quantitative immunohistochemistry in the entorhinal cortex from Alzheimer patients and age-matched controls. We observed a significant decrease in presynaptic synaptophysin and an increase in postsynaptic density protein PSD-95, positively correlated with beta amyloid and phosphorylated Tau proteins in Alzheimer cases. Furthermore, Alzheimer-like neuritic retraction was generated in okadaic acid (OA) treated SH-SY5Y neuroblastoma cells with no decrease in PSD-95 expression. However, in a SH-SY5Y clone with decreased expression of transcription regulator LMO4 (as observed in Alzheimer's disease) and increased neuritic length, PSD-95 expression was enhanced but did not change with OA treatment. Therefore, increased PSD-95 immunoreactivity in the entorhinal cortex might result from compensatory mechanisms, as in the SH-SY5Y clone, whereas increased Alzheimer-like Tau phosphorylation is not related to PSD-95 expression, as suggested by the OA-treated cell models.

Produção e qualidade do grão do arroz irrigado infestado por adultos de percevejo-das-panículas

O objetivo deste trabalho foi comparar os danos qualitativos e quantitativos, causados por adultos de Oebalus poecilus (Dallas) Stal, em panículas de 39 genótipos de arroz irrigado. Em campo, as panículas emergentes foram isoladas em gaiolas e infestadas com dois insetos, no início da fase leitosa das espiguetas. Panículas não infestadas serviram de testemunha. Após a colheita, amostras compostas de 50 espiguetas de cada grau de infestação, para cada genótipo, foram semeadas em telado, e a emergência foi determinada após 16 dias. Manchas no grão foram avaliadas em amostras de 50 espiguetas. O percevejo provocou alterações significativas, pois reduziu a massa e o número de espiguetas por panícula, a porcentagem de plântulas emergidas, e aumentou a porcentagem de espiguetas vazias e com grão manchado. A combinação da porcentagem de perda de massa com a de sementes inviáveis foi de 44%, e da perda de massa com a de espiguetas manchadas, de 81,4%. A maior porcentagem de plântulas emergidas de espiguetas manchadas ocorreu nos genótipos de ciclo médio. Os genótipos de ciclo curto CNAi 8859, CNAi 8879, CNAi 8885 e CNAi 8886, e os de ciclo médio CNAi 9089, CNAi 9097, CNAi 9150, CNAi 9687 CNAi 9730, CNAi 9747 e CNAi 9778 são os mais tolerantes ao percevejo-das-panículas.

Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein

We investigated how synaptic plasticity is related to the neurodegeneration process in the human dorsolateral prefrontal cortex. Pre- and postsynaptic proteins of Brodmann's area 9 from patients with Alzheimer's disease (AD) and age-matched controls were quantified by immunohistochemical methods and Western blots. The main finding was a significant increase in the expression of postsynaptic density protein PSD-95 in AD brains, revealed on both sections and immunoblots, while the expression of spinophilin, associated to spines, remained quantitatively unchanged despite qualitative changes with age and disease. Presynaptic protein alpha-synuclein indicated an increased immunohistochemical level, while synaptophysin remained unchanged. MAP2, a somatodendritic microtubule protein, as well as AD markers such as amyloid-beta protein and phosphorylated protein tau showed an increased expression on immunosections in AD. Altogether these changes suggest neuritic and synaptic reorganization in the process of AD. In particular, the significant increase in PSD-95 expression suggests a change in NMDA receptors trafficking and may represent a novel marker of functional significance for the disease.

Seletividade de agrotóxicos usados na produção integrada de maçã para adultos de Trichogramma pretiosum

O objetivo deste trabalho foi avaliar a seletividade de 12 agrotóxicos usados na produção integrada de maçã, em laboratório (temperatura 25±1ºC, umidade relativa 70±10% e fotófase de 14 horas), tendo-se exposto adultos de Trichogramma pretiosum a resíduos secos dos agrotóxicos, na máxima dosagem recomendada para uso em campo, e tendo-se posteriormente mensurado o número de ovos parasitados por fêmea. Reduções no parasitismo, em relação à testemunha (água), foram utilizadas para classificar os agrotóxicos em inócuo (<30%), levemente nocivo (30-79%), moderadamente nocivo (80-99%) e nocivo (>99%). Foram inócuos os acaricidas Envidor (espirodiclofeno), Kendo 50 SC (fenpiroximato) e Ortus 50 SC (fenpiroximato), os fungicidas Antracol 700 PM (propinebe), Midas BR (famoxadona + mancozebe), Palisade (fluquinconazol), Persist SC (mancozebe) e Systhane PM (miclobutanil) e o inseticida Mimic 240 SC (tebufenozida); o herbicida Polaris (glifosato) foi levemente nocivo; os herbicidas Finale (glufosinato sal de amônio) e Roundup Original (glifosato) foram moderadamente nocivos a T. pretiosum.

Visual cortex in Alzheimer's disease: occurrence of neuronal death and glial proliferation, and correlation with pathological hallmarks.

Visual areas 17 and 18 were studied with morphometric methods for numbers of neurons, glia, senile plaques (SP), and neurofibrillary tangles (NFT) in 13 cases of Alzheimer's disease (AD) as compared to 11 controls. In AD cases, the mean neuronal density was significantly decreased by about 30% in both areas 17 and 18, while the glial density was increased significantly only in area 17. The volume of area 17 was unchanged in AD cases but its total number of neurons was decreased by 33% and its total number of glia increased by 45% compared to controls. In AD the number of SP was similar in areas 17 and 18, while that of NFT was significantly higher in area 18. The number of neurons with NFT was only 2% in area 17 and about 10% in area 18. The discrepancy between the loss of neurons and the amount of NFT suggests that neuronal loss can occur without passing through NFT degeneration. The deposition of SP was correlated with glial proliferation, but not with neuronal loss or neurofibrillary degeneration.

Composição tecidual dos cortes da carcaça de ovinos jovens e adultos

O objetivo deste trabalho foi avaliar a composição tecidual dos cortes da carcaça de ovinos jovens e adultos. Utilizaram-se 36 animais ½ Ile de France ½ Ideal (12 cordeiros não castrados, 12 ovelhas e 12 capões). Os animais foram criados em pasto de Tifton-85 e suplementados com concentrado em 1% em relação ao peso corporal. Os cordeiros foram desmamados com aproximadamente 17±0,87 kg de peso corporal e abatidos aos 32 kg, com aproximadamente cinco meses de idade; as ovelhas e os capões foram abatidos com aproximadamente 55±1,26 kg e 60 meses de idade. O corte da carcaça com maior porcentual de músculos foi o da perna, seguido da paleta e do lombo, entre as categorias animais estudadas. Os cordeiros apresentaram o maior porcentual de ossos, nos cortes da carcaça estudados, do que os animais adultos. As gorduras subcutânea, intermuscular e total, dos cortes da carcaça, foram maiores nos animais adultos do que nos jovens, e o lombo teve maior porcentual de gordura total, seguido da paleta e da perna. Concluiu-se que as categorias animais influenciam a composição tecidual dos cortes da carcaça, e o tecido adiposo é um dos principais responsáveis por tais diferenças.

Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.