Therapies of neurodegenerative diseases are often very difficult and their success depend on an early diagnose. From that reason we have been developing new diagnostic method for multiple sclerosis and Alzheimer disease by drop coating deposition Raman (DCDR) spectroscopy of cerebrospinal fluid (CSF) in this work. We found out conditions of measurements, where spectra were reproducible and accepted for standard diagnostic practices. We discovered that CSF has fast degradation at a room temperature, which was detectable in spectra after 5 hours, and degradation due to refreezing. DCDR spectra of CSF from individual patients were analyzed by factor and cluster analysis. Multiple sclerosis was manifested by lower intensity of a Raman band at 1080 cm−1 , which is probably connected with more general pathologic state. Spectral changes caused by Alzeheimer disease were more complex and beside changes mentioned above also changes connected with composition and conformation of proteins were identified in regions 1200-1800 cm−1 and 2870-2950 cm−1 . Additionally, we succeeded in distinguishing of young healthy patients from older patients in DCDR spectra. In this work were checked up, that DCDR is good diagnostic method for clinical practices for determining neurodegenerative diseases through the complex...

Animal models of Alzheimer's disease display cognitive insufficiencies which mimic human symptoms and occur at a given age or post-treatment time. Animals are typically tested using canonical behavioral tests, lasting minutes and taking place mostly in the non-active period of the daily cycle. Animals are exposed to certain amounts of manipulation-induced stress. Our work represents a validation study for the rat behavioral system IntelliCage. The tested individuals live freely in a group and their behavior is monitored continuously. It is however possible to set up individual tests for each animal or a group of animals. The rats are not subject to human manipulation and hence the results are not affected by manipulation-induced stress. We tested early cognitive impairment in the transgenic rat model TgF344-AD at 6 - 8 months of age. Further, we tested two most common protocols of the streptozotocin model, i.e. single dose of intracerebroventricular 3 mg/kg streptozotocin and double dose 48 hrs apart. Results were compared with the canonical Morris Water Maze (MWM) test. In the MWM test, transgenic animals did not differ from controls in any of the studied parameters. The streptozotocin model displayed a deficit only in the double dose group. However in the IntelliCage, transgenic animals displayed...

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[pt] Diante do cenário epidêmico das demências e do crescente envelhecimento populacional, esta pesquisa teve como foco o desenvolvimento de produtos e serviços reabilitadores e preventivos do Alzheimer para/com idosos institucionalizados. O objetivo do estudo foi melhorar a cognição e a qualidade de vida dos hóspedes, bem como valorizar seu papel social. Quanto à estrutura, a pesquisa se articulou em 5 etapas: (1) revisão bibliográfica sobre memória, processos cognitivos e Alzheimer; (2) estudo de caso no Bem Viver, que cumulou: observações das atividades, da rotina e das respostas dos idosos aos estímulos aplicados, entrevistas com os hóspedes, funcionários e familiares, e desenvolvimento de conceitos projetuais voltados à criação de produtos e serviços com foco no Alzheimer e na institucionalização; (3) cocriação de artefatos interdisciplinares e multifacetados em parceira com os profissionais da casa, amparada pela ferramenta Card Sorting e por um diagrama interdisciplinar; (4) implementação dos produtos e serviços pelos funcionários da casa nas atividades do Bem Viver; e (5) identificação dos resultados dos estímulos na cognição e na qualidade de vida dos idosos, mediante comparação dos dados coletados no momento inicial e final da pesquisa. No desfecho desta investigação, observou-se que os artefatos em formato aberto e as oficinas foram capazes de melhorar a orientação temporal e as habilidades de escrita e de cálculo de idosos, bem como permitiram despertar a criatividade dos hóspedes, fortalecer os laços de amizade e estimular memórias e funções mentais de indivíduos com os mais variados tipos de demência e perfis cognitivos. / [en] Taking into account the epidemic scenario of dementias and the increased growth of the elderly population, this research consisted of proposing products and services for both recovery and prevention of the Alzheimer s disease among institutionalized elderly. The aim of this study was to enhance cognition and the quality of life of patients, as well as promoting their social role. Regarding structure, this project was organized around 5 stages: (1) a bibliographic review on memory, cognitive processes and the Alzheimer s disease; (2) a case study at the nursing home Centro de Atividades Bem Viver that included observations of activities, routine, and the elderly responses to the stimuli applied; interviews with the guests, employees and relatives; and the development of design concepts for the creation of products and services that focused on the Alzheimer s disease and institutionalization; (3) cocreation of interdisciplinary and multifaceted artifacts in partnership with the instructors of the institution, as well as the support of Card Sorting and an interdisciplinary diagram; (4) implementation of products and services by the staff of the nursing home in the activities at Bem Viver; and (5) identification of results, with respect to cognition and quality of life, by drawing a comparison of the data gathered early and later on. At the end, it was possible to assess that the open-design objects and the workshops improved spatial orientation and also the elderly s writing and math skills, along with the guests creative awakening, the strengthening of friendship ties and the stimulation of memories and mental functions of individuals with different types of dementia and cognitive profiles.

<p>Human disease and the corresponding immune response occur in three-dimensional space and time. Many diseases are difficult to study, either <em>in vivo</em> or <em>in vitro</em>, due to the complexity of the system. Despite computational models that can address complexity, many do not capture the spatial  aspects  of  disease.  Agent-based  models  are  mechanistic,  spatiotemporal  computational models that can be integrated with other mathematical models to create multiscale models. Here I detail two models to examine spatiotemporal progression and possible treatment strategies for two diseases  with  low  treatment  success: <em>Mycobacterium  avium complex</em>  (MAC)  and  Alzheimer’s Disease.</p> <p>MAC  are  biofilm-forming  environmental  microbes  capable  of  residing  in  human  lung nodules,  causing  MAC  pulmonary  disease  (MAC-PD).  Clinical  drug  susceptibility  tests  and treatment  outcomes  are  poorly  correlated,  and  nodules  are  complex  and  difficult  to  monitor, leading to low MAC cure rates (45-65%)². I have developed an informative model of the initial infection  events  in  MAC-PD. This  model  has  been  used  to  probe  many  different  scenarios  of infection and to predict the effect of potential interventions.</p> <p>Alzheimer’s  Disease  (AD)  is  the  leading  cause  of  dementia,  with  no  disease-altering pharmacological  intervention.  Microglia  are  phagocytotic  neuroimmune  cells,  known  to  form barriers around plaques. There has been increased interest in leveraging microglia to slow the progression of neurodegeneration by manipulating these barriers. I present an agent-based model of microglia barriers at the single plaque level and use knock-out experiments to probe possible targets for immunotherapy and quantify their effects on plaque progression.</p>

No / OBJECTIVES: To describe ways of coping in people with mild to moderate AD when faced with situations that are challenging to their memory. METHOD: Twenty-four participants (12 with mild and 12 with moderate AD) were presented with a set of seven tasks that were analogues of everyday situations that tax memory. The participants' responses were videotaped and analysed. RESULTS: Participants' coping responses were grouped into seven categories to best reflect the main strategies. Individuals used a significantly greater frequency of effortful problem solving (self-reliance and reliance on carers) (p < 0.01) than other ways of coping. Positive acknowledgement of memory difficulties was used significantly more than negative acknowledgement and defensive coping (concealment and avoidance) (p < 0.01). CONCLUSION: This study used novel methodology of observation of behavioural responses in analogues of everyday situations. The predominance of effortful problem-solving emphasizes the role of the person with AD as an active agent in the management of memory loss. An emphasis in previous literature on defensive coping and denial is counter-balanced by the finding that participants commonly coped by acknowledging their memory impairment.

<p dir="ltr">Neurodegenerative diseases are progressive, incurable conditions that affect tens of millions of people worldwide and are characterized by the aggregation of misfolded protein in the brain. Though the precise role of these amyloid aggregates in the onset and progression of these diseases is not clear at this time, there is a pressing need to understand how they form and spread in human disease. In service to these aims, I have conducted three small projects to expand knowledge in this regard. I first investigated the use of thioflavin T, a common amyloid stain, as an affinity reagent for the general purification of amyloid filaments from <i>ex vivo </i>samples, observing strong potential using a relatively simple, inexpensive magnetic bead conjugation technique. I next analyzed the formation of filaments of a truncated recombinant amyloid-beta peptide with residues 1-35, observing a new filament type formed at low pH in the wild-type sequence of this truncated peptide. Finally, I conducted structural studies on amyloid-beta(1-42) filaments prepared under different conditions consistent with traumatic brain injury to observe their effect on amyloid folding. While I found no effect of differential conditions on filament type, the low-resolution structures solved were highly consistent with aggregates found in Alzheimer’s disease patients, presenting a promising way forward for <i>in vitro</i> modeling of amyloid filaments that are true to pathology. In sum, the work here presented advances the concepts of both how amyloid aggregates from patient brains can be best prepared for structural analysis, and the factors underpinning their aggregation at the onset of neurodegenerative disease.</p>