Matching Items (63)

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Assisted Cycle Therapy (ACT) Did Not Improve Depression in Older Adults with Down Syndrome

Description

The purpose of this study was to examine the influence of Assisted Cycling Therapy (ACT) on depression in older adults with Down Syndrome (DS). We predicted that older adults with Down Syndrome would see an improvement in their depressive symptoms

The purpose of this study was to examine the influence of Assisted Cycling Therapy (ACT) on depression in older adults with Down Syndrome (DS). We predicted that older adults with Down Syndrome would see an improvement in their depressive symptoms after ACT and Voluntary Cycling (VC). However, we predicted there would be a greater improvement in depressive symptoms after ACT in comparison to VC. Depression was measured using a modified version of the Children's Depression Inventory 2 (CDI 2) due to the low mental age of our participant population. Twenty-one older adults with DS were randomly assigned to one of three interventions, which took place over an eight-week period of time. Eleven older adults with DS completed the ACT intervention, which is stationary cycling on a recumbent bicycle with the assistance of a motor to maintain a cadence at least 35% greater than the rate of voluntary cycling. Nine participants completed the voluntary cycling intervention, where they cycled at a cadence of their choosing. One participant composed our no cycling control group. No intervention group reached results that achieved a conventional level of significance. However, there was a trend for depression to increase after 8 weeks throughout all three intervention groups. We did see a slightly slower regression of depression in the ACT group than the VC and control. Our results were discussed with respect to social and cognitive factors relevant to older adults with DS and the subjective nature of the CDI2. This study brings attention to the lack of accurate measures and standardized research methods created for populations with intellectual disabilities in regards to research.

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2018-05

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Engineering a Human Induced Pluripotent Stem Cell (hiPSC)-Based Model of Alzheimer's Disease

Description

Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal

Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.

Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.

It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.

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2018-05

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Assessing the Influence of Extracellular Mitochondria on Neuroinflammation

Description

A prominent aspect of Alzheimer’s disease (AD) is the presence of neuroinflammation is mediated by the activation of microglial cells, which are the immune cells in the central nervous system (CNS) that express an array of cytokines that may promote

A prominent aspect of Alzheimer’s disease (AD) is the presence of neuroinflammation is mediated by the activation of microglial cells, which are the immune cells in the central nervous system (CNS) that express an array of cytokines that may promote an inflammatory response. The main cytokines produced are: tumor necrosis factor-alpha (TNF-), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The presence of these cytokines in the CNS may lead to neuronal death, to the production of toxic chemicals (such as nitric oxide), and to the generation of amyloid beta (a major pathological feature of AD). Previous studies have shown that modulation of the inflammatory response in the nervous system can potentially prevent and/or delay the onset of neurodegenerative diseases such as AD. Therefore, it is important to identify the process that induces CNS inflammation. For example, mitochondrial lysates have been found to produce an inflammatory response due to their ability to stimulate TNF-, Aβ, and APP mRNA [10]. Interestingly, extracellular mitochondria have been detected in the brain due to neurons degrading old mitochondria extracellularly. Therefore, we set out to study the effect of whole mitochondria isolated by differential centrifugation from human neuroblastoma cells (BE(2)-M17 cells) on the neuroinflammatory response in a human microglia model (THP-1 cells). Despite our best efforts, in the end it was unclear whether the mitochondrial fraction or other cellular components induced the inflammatory response we observed. Thus, further work with an improved mitochondrial isolation method should be carried out to address this issue.

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2018-05

Acute tau knockdown in the hippocampus of adult mice causes learning and memory deficits

Description

To date, it has been difficult to elucidate the role of tau in learning and memory during adulthood due to developmental compensation of other microtubule associated proteins in Tau knockout (KO) mice. Here, we generated an adeno-associated virus (AAV) expressing

To date, it has been difficult to elucidate the role of tau in learning and memory during adulthood due to developmental compensation of other microtubule associated proteins in Tau knockout (KO) mice. Here, we generated an adeno-associated virus (AAV) expressing a doxycycline (doxy)-inducible short-hairpin (sh) RNA targeted to tau, and stereotaxically and bilaterally injected 7-month-old C57BL/6 mice with either the AAV-shRNAtau or an AAV expressing a scramble shRNA sequence. Seven days after the injections, all animals were administered doxy for thirty-five days to induce expression of shRNAs, after which they were tested in the open field, rotarod and Morris water maze (MWM) to assess anxiety like behavior, motor coordination and spatial reference memory, respectively. Our results show that reducing tau in the adult hippocampus produces significant impairments in motor coordination, endurance and spatial memory. Tissue analyses shows that tau knockdown reduces hippocampal dendritic spine density and the levels of BDNF and synaptophysin, two proteins involved in memory formation and plasticity. Our approach circumvents the developmental compensation issues observed in Tau KO models and shows that reducing tau levels during adulthood impairs cognition.

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2018-05

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Comparing Protocols for Extracting, Amplifying, and Imaging ApoE ε4 Allele: Preliminary work for understanding Alzheimer’s Disease in asymptomatic individuals

Description

This thesis aimed to develop a consistent protocol used to effectively image the apolipoprotein E (ApoE) ε4 allele, which is a known genetic risk factor for Alzheimer’s Disease (AD). The research team used methods to extract DNA from saliva samples,

This thesis aimed to develop a consistent protocol used to effectively image the apolipoprotein E (ApoE) ε4 allele, which is a known genetic risk factor for Alzheimer’s Disease (AD). The research team used methods to extract DNA from saliva samples, amplify the DNA using polymerase chain reaction (PCR), and image the results using gel electrophoresis and a transilluminator. Extensive literature review was used to optimize these techniques. Future studies will use these methods of characterizing the ApoE ε4 allele as preliminary work towards the goal of integrating this protocol into ongoing research in aging within the Motor Rehabilitation and Learning (MRL) Lab on Arizona State University’s campus.

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2019-05

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Cell labeling techniques to assess Alzheimer's disease model

Description

Effectively modeling Alzheimer’s disease will lend to a more comprehensive
understanding of the disease pathology, more efficacious drug development and
regenerative medicine as a form of treatment. There are limitations with current
transgenic mouse models of Alzheimer’s disease and the

Effectively modeling Alzheimer’s disease will lend to a more comprehensive
understanding of the disease pathology, more efficacious drug development and
regenerative medicine as a form of treatment. There are limitations with current
transgenic mouse models of Alzheimer’s disease and the study of post mortem brain tissue of Alzheimer’s diseases patients. Stem cell models can overcome the lack of clinical relevance and impracticality associated with current models. Ideally, the use of stem cell models provides the foundation to study the biochemical and physiological aspects of Alzheimer’s disease, but at the cellular level. Moreover, the future of drug development and disease modeling can be improved by developing a reproducible and well-characterized model of AD that can be scaled up to meet requirements for basic and translational applications. Characterization and analysis of a heterogenic neuronal culture developed from induced pluripotent stem cells calls for the understanding of single cell identity and cell viability. A method to analyze RNA following intracellular sorting was developed in order to analyze single cell identity of a heterogenic population
of human induced pluripotent stem cells and neural progenitor cells. The population was intracellularly stained and sorted for Oct4. RNA was isolated and analyzed with qPCR, which demonstrated expected expression profiles for Oct4+ and Oct4- cells. In addition, a protocol to label cells with pO2 sensing nanoprobes was developed to assess cell viability. Non-destructive nanoprobe up-take by neural progenitor cells was assessed with fluorescent imaging and flow cytometry. Nanoprobe labeled neurons were cultured long-term and continued to fluoresce at day 28. The proof of concept experiments demonstrated will be further expanded upon and utilized in developing a more clinically relevant and cost-effective model of Alzheimer’s disease with downstream applications
in drug development and regenerative medicine.

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2019-05

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Alzheimer's Stigma in Guatemala

Description

ABSTRACT
Overview: There has been very little research done into the topic of mental illness in general, and Alzheimer’s Disease specifically, in Guatemala. The existing research accounts for prevalence of mental illness in Guatemala with an estimated prevalence of

ABSTRACT
Overview: There has been very little research done into the topic of mental illness in general, and Alzheimer’s Disease specifically, in Guatemala. The existing research accounts for prevalence of mental illness in Guatemala with an estimated prevalence of a mental illness of 27.8% (Guatemalan Government, 2009). Alzheimer’s Disease is less well researched.

Research Question: This research addresses this gap in knowledge by focusing on the stigma felt toward people who had Alzheimer’s Disease and Related Dementia (ADRD) by the people of Guatemala.

Participants: One-hundred twenty-four individuals over the age of 18 were recruited for participation. Participants were recruited through opportunity samples in artisan markets in Antigua.

Procedures: Participants completed a survey including demographic questions, the Dementia Attitudes Scale (O’Connor & McFadden 2010), as well as open-ended questions regarding the causes, symptoms, and treatments for Alzheimer’s. The study was conducted from July 2, 2018 to August 2, 2018.

Results: The average DAS score of 100.31± 14.01 found in this study is similar to results from other studies conducted in the United States (O'Connor & McFadden, 2010). Factor analysis did not verify the existence of sub-scales in the survey, as found in previous studies. The free-response questions indicated that many people may believe that ADRD is an inherited disease or one that is caused by factors outside of their control.

Conclusions: The high DAS score of 100.31± 14.01 matches other studies that used the DAS. Scores of 103.51± 13.43 (Scerri & Scerri, 2013) were reported in other studies and interpreted as positive as it relates to stigma. This points to a low stigma level in Guatemala. The failure to verify the sub-scales leads to the conclusion that although scales are validated in western nations, they may not be culturally portable. The DAS scale may not be measuring the same thing in this sample’s population versus previous studies sample populations.

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2019-05

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What Works Best? A Global Comparative-Analysis of Alzheimer’s Disease Treatment and Care

Description

The purpose of this project is to present research within three main categories of treatment and care such as exercise, socialization and alternative therapies (art, pet, and reminiscent therapies) for Alzheimer’s Disease (AD). These categories will be examined in the

The purpose of this project is to present research within three main categories of treatment and care such as exercise, socialization and alternative therapies (art, pet, and reminiscent therapies) for Alzheimer’s Disease (AD). These categories will be examined in the following countries: United Kingdom, United States, Brazil, and China. Then, the synthesized material will be analyzed and placed into a comparison and contrast model showcasing what each country is currently using and the success of the particular resource within a heat map. According to the research found on the following categories of exercise, socialization and alternative therapies, I will conclude that a combination of aerobic and resistance training, routine support groups and art/pet therapies are the most effective treatment options against Alzheimer’s Disease.

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2019-05

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The Relationship between Wastewater Toxic Substances and Alzheimer’s disease

Description

Alzheimer’s disease (AD) is a neurodegenerative disease resulting in loss of cognitive function and is not considered part of the typical aging process. Recently, research is being conducted to study environmental effects on AD because the exact molecular mechanisms behind

Alzheimer’s disease (AD) is a neurodegenerative disease resulting in loss of cognitive function and is not considered part of the typical aging process. Recently, research is being conducted to study environmental effects on AD because the exact molecular mechanisms behind AD are not known. The associations between various toxins and AD have been mixed and unclear. In order to better understand the role of the environment and toxic substances on AD, we conducted a literature review and geospatial analysis of environmental, specifically wastewater, contaminants that have biological plausibility for increasing risk of development or exacerbation of AD. This literature review assisted us in selecting 10 wastewater toxic substances that displayed a mixed or one-sided relationship with the symptoms or prevalence of Alzheimer’s for our data analysis. We utilized data of toxic substances in wastewater treatment plants and compared them to the crude rate of AD in the different Census regions of the United States to test for possible linear relationships. Using data from the Targeted National Sewage Sludge Survey (TNSSS) and the Centers for Disease Control and Prevention (CDC), we developed an application using R Shiny to allow users to interactively visualize both datasets as choropleths of the United States and understand the importance of this area of research. Pearson’s correlation coefficient was calculated resulting in arsenic and cadmium displaying positive linear correlations with AD. Other analytes from this statistical analysis demonstrated mixed correlations with AD. This application and data analysis serve as a model in the methodology for further geospatial analysis on AD. Further data analysis and visualization at a lower level in terms of scope is necessary for more accurate and reliable evidence of a causal relationship between the wastewater substance analytes and AD.
GitHub Repository: https://github.com/komal-agrawal/AD_GIS.git

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2019-05

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Removing Neuronal PRAS40 Exacerbates Alzheimer's Disease Pathology in a Mouse Model

Description

Alzheimer’s disease (AD) is characterized by the aberrant accumulation and aggregation of proteins that in turn contribute to learning and memory deficits. The mammalian target of rapamycin (mTOR) plays an essential role in regulating the synthesis and degradation of proteins

Alzheimer’s disease (AD) is characterized by the aberrant accumulation and aggregation of proteins that in turn contribute to learning and memory deficits. The mammalian target of rapamycin (mTOR) plays an essential role in regulating the synthesis and degradation of proteins that contribute to cell growth and learning and memory. Hyperactivity of mTOR can cause detrimental effects to protein homeostasis and has been linked to AD. The proline-rich Akt-substrate 40 kDa (PRAS40) is a negative regulator of mTOR, as it binds to mTOR directly, reducing its activity. Upon phosphorylation, PRAS40 detaches from mTOR thereby releasing its inhibitory effects. Increased phosphorylation of PRAS40, and a subsequent increase in mTOR activity has been linked to diabetes, cancer, and other conditions; however, PRAS40’s direct role in the pathogenesis of AD is still unclear. To investigate the role of PRAS40 in AD pathology, we generated a PRAS40 conditional knockout mouse model and, using a neuronal-specific Cre recombinase, selectively removed PRAS40 from APP/PS1 mice. Removing neuronal PRAS40 exacerbated Abeta levels and plaque load but paradoxically had no significant effects on mTOR signaling. Mechanistically, the increase in Abeta pathology was linked to a decrease in autophagy function. Our data highlight a primary role of PRAS40 in the pathogenesis of AD.

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2019-05