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- Title
- DISSECTING THE MECHANISTIC ROLES OF REGULATORS IN MEDIATING AMYLOID-BETA AMYLOIDOGENESIS.
- Creator
- Shen, Fengyun, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Alzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and...
Show moreAlzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and carnosine, phospholipids, and β-hairpins on Aβ aggregation to dissect their mechanistic roles in the amyloidogenesis of Aβ. We first systematically studied the kinetic impact of Zn2+ on the aggregation of Aβ40 and Aβ40-M. Our results show that the presence of Zn2+ transforms the Aβ40 aggregation kinetics from a single sigmoidal to a biphasic process, while the aggregation of Aβ40-M is significantly suppressed by Zn2+. We also found that a nature dipeptide, carnosine, remarkably decreases the activity of Zn2+ on modulating Aβ aggregation, although it has a weak direct effect on the peptide aggregation kinetics. Second, we investigated the activities of Aβ40 and Aβ42 in inducing membrane damage and the effects of lipid membranes on the aggregation of these peptides using liposome models containing mitochondrial-specific phospholipid–cardiolipin (CL).
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014314
- Subject Headings
- Alzheimer's disease, Amyloid beta-Peptides, Neurodegenerative Diseases
- Format
- Document (PDF)
- Title
- Studying the Effects of Lipid Membranes and Polysaccharides on the Amyloidogenicity of Fragments of Amyloid Beta.
- Creator
- Petersen, Katherine, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
The amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely...
Show moreThe amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely resulting in the etiology of AD. In this study, two fragments are used, the 23-residue N-terminal fragment, Aβ23 and the 30-residue C-terminal fragment, Aβ11-40, to better understand the role of the N and C-terminus in the aggregation of Aβ peptide. Aβ11-40 has also been found in the brains of AD patients, playing a biological role in the disease. This study used analytical and biophysical techniques to systematically synthesize, purify, characterize, and study these fragments' aggregation in different conditions. We investigated the effects of lipid membranes on the aggregation of Aβ23 and Aβ11-40 and the activities of these peptides in inducing membrane damage. The results show that the aggregation of Aβ23 was increased in the presence of lipid membranes, likely due to favorable electrostatic interactions. However, the aggregation of Aβ11-40 was not influenced by lipid membranes. A dye leakage study was carried out to study the membrane damage occurring as a result of fragments' interaction with lipid membranes. The results showed that neither fragment had a profound effect on membrane destruction, although the charge of the lipid head seemed to play a role. This work's second study focused on the effect of three specific polysaccharides, heparin, chitosan (CHT), and trimethyl chitosan (TMC), on the aggregation of Aβ23 and Aβ11-40. The results showed that for Aβ23, heparin increased aggregation, while both CHT and TMC decreased aggregation. However, for Aβ11-40, both heparin and CHT did not affect aggregation, while TMC decreased aggregation.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014294
- Subject Headings
- Amyloid beta-Peptides, Alzheimer's disease
- Format
- Document (PDF)
- Title
- Applying Story-Guided Dialogue to Examine Social Connections for Rural Caregivers of Persons Living with Alzheimer’s Disease and Related Dementias During A Global Pandemic.
- Creator
- Cappo, Kathleen, Wiese, Lisa Kirk, Florida Atlantic University, Christine E. Lynn College of Nursing, Christine E. Lynn College of Nursing
- Abstract/Description
-
In the U.S., an estimated 16 million persons provide unpaid care for family and friends with Alzheimer’s disease and related dementias (ADRD). These caregivers are experiencing challenges, such as lack social interaction, which further impacts their own health. Social isolation for caregivers is now considered to be another challenge due to living in a global pandemic. The purpose of this study was to address the gap in understanding rural informal caregiver by examining social connectedness...
Show moreIn the U.S., an estimated 16 million persons provide unpaid care for family and friends with Alzheimer’s disease and related dementias (ADRD). These caregivers are experiencing challenges, such as lack social interaction, which further impacts their own health. Social isolation for caregivers is now considered to be another challenge due to living in a global pandemic. The purpose of this study was to address the gap in understanding rural informal caregiver by examining social connectedness through the use of story-guided dialogues among rural caregivers of PWD during a global pandemic. Story Theory guides intentional dialogue, to bring forward connecting with self-in-relation through use of story path, noting low, high, and turning points.
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FA00013983
- Subject Headings
- Caregivers, Rural caregivers, Alzheimer's disease, Social isolation, Pandemics
- Format
- Document (PDF)
- Title
- DISCOVERY OF GENES AND MOLECULAR PROCESSES THAT ARE IMPORTANT FOR THE PATHOGENESIS OF ALZHEIMER’S DISEASE.
- Creator
- Kwakye, Alexander, Li, Zhongwei, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
- Abstract/Description
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Alzheimer’s Disease (AD) is a complex brain disorder that affects at least one in every ten persons aged 65 and above worldwide. The pathogenesis of this disorder remains elusive. In this work, we utilized a rich set of publicly available gene expression data to elucidate the genes and molecular processes that may underlie its pathogenesis. We developed a new ranking score to prioritize molecular pathways enriched in differentially expressed genes during AD. After applying our new ranking...
Show moreAlzheimer’s Disease (AD) is a complex brain disorder that affects at least one in every ten persons aged 65 and above worldwide. The pathogenesis of this disorder remains elusive. In this work, we utilized a rich set of publicly available gene expression data to elucidate the genes and molecular processes that may underlie its pathogenesis. We developed a new ranking score to prioritize molecular pathways enriched in differentially expressed genes during AD. After applying our new ranking score, GO categories such as cotranslational protein targeting to membrane, SRP-dependent cotranslational protein targeting to membrane, and spliceosomal snRNP assembly were found to be significantly associated with AD. We also confirm the protein-protein interaction between APP, NPAS4 and ARNT2 and explain that this interaction could be implicated in AD. This interaction could serve as a theoretical framework for further analyses into the role of NPAS4 and other immediate-early genes in AD pathogenesis.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013541
- Subject Headings
- Alzheimer's disease, Alzheimer's disease--Genetic aspects, Alzheimer's disease--Molecular aspects, Alzheimer's disease--Pathogenesis
- Format
- Document (PDF)
- Title
- STREAMLINING CLINICAL DETECTION OF ALZHEIMER’S DISEASE USING ELECTRONIC HEALTH RECORDS AND MACHINE LEARNING TECHNIQUES.
- Creator
- Kleiman, Michael J., Barenholtz, Elan, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
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Alzheimer’s disease is typically detected using a combination of cognitive-behavioral assessment exams and interviews of both the patient and a family member or caregiver, both administered and interpreted by a trained physician. This procedure, while standard in medical practice, can be time consuming and expensive for both the patient and the diagnostician especially because proper training is required to interpret the collected information and determine an appropriate diagnosis. The use of...
Show moreAlzheimer’s disease is typically detected using a combination of cognitive-behavioral assessment exams and interviews of both the patient and a family member or caregiver, both administered and interpreted by a trained physician. This procedure, while standard in medical practice, can be time consuming and expensive for both the patient and the diagnostician especially because proper training is required to interpret the collected information and determine an appropriate diagnosis. The use of machine learning techniques to augment diagnostic procedures has been previously examined in limited capacity but to date no research examines real-world medical applications of predictive analytics for health records and cognitive exam scores. This dissertation seeks to examine the efficacy of detecting cognitive impairment due to Alzheimer’s disease using machine learning, including multi-modal neural network architectures, with a real-world clinical dataset used to determine the accuracy and applicability of the generated models. An in-depth analysis of each type of data (e.g. cognitive exams, questionnaires, demographics) as well as the cognitive domains examined (e.g. memory, attention, language) is performed to identify the most useful targets, with cognitive exams and questionnaires being found to be the most useful features and short-term memory, attention, and language found to be the most important cognitive domains. In an effort to reduce medical costs and streamline procedures, optimally predictive and efficient groups of features were identified and selected, with the best performing and economical group containing only three questions and one cognitive exam component, producing an accuracy of 85%. The most effective diagnostic scoring procedure was examined, with simple threshold counting based on medical documentation being identified as the most useful. Overall predictive analysis found that Alzheimer’s disease can be detected most accurately using a bimodal multi-input neural network model using separated cognitive domains and questionnaires, with a detection accuracy of 88% using the real-world testing set, and that the technique of analyzing domains separately serves to significantly improve model efficacy compared to models that combine them.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013326
- Subject Headings
- Alzheimer's disease, Electronic Health Records, Machine learning
- Format
- Document (PDF)
- Title
- Role of the N-Terminal Hydrophilic Region of Amyloid Beta Peptide in Amyloidogenesis, Membrane Interaction and Toxicity Associated with Alzheimer’s Disease.
- Creator
- Morris, Clifford M., Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Alzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain...
Show moreAlzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain understanding on the electrostatic and hydrophobic constituents of the mechanism. This was achieved by substituting specific charged residues located in the NTR of Aβ40 and investigating their effects through a variety of techniques. We also investigated the role of NTR charged residues in their interaction with supported phospholipid bilayer membranes through the use of Quartz Crystal Microbalance with Dissipation (QCM-D) monitoring to gain insight on the mechanistic details of the interaction. To further understand the implications of substituting charged NTR residues on membrane interaction, pore formation and damage, we utilized a carboxyfluorescein dye leakage assay to quantify the membrane damage caused by Aβ40 and the NTR mutants. We also performed neurotoxicity assay with SH-SY5Y neuroblastoma cells to shed light on the effects of NTR substitutions on cellular toxicity. Finally, we synthesized a polymer, trimethyl chitosan (TMC), and utilized it as a polyelectrolyte monitor of electrostatic interactions occurring between TMC and the NTR of Aβ40. Our results demonstrate that the NTR charged residues of Aβ40 contribute significantly to the aggregation process, amyloidogenesis, and phospholipid membrane interaction and perturbation by means of electrostatic, thermodynamic and hydrophobic forces.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013246
- Subject Headings
- Alzheimer's disease, Amyloid beta-Peptides, Amyloid
- Format
- Document (PDF)
- Title
- Aggregation Inhibition and Detection of Alzheimer’s Amyloidogenic and Oligomeric Peptides.
- Creator
- Elbassal, Esmail A. E., Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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Protein aggregation, oligomer and fibril formation is one of the dominant characteristics in the pathogenesis of a number of neurodegenerative diseases, such as Alzheimer’s disease (AD). Inhibition of toxic oligomer and fibril formation is one of the approaches to find potential drug candidates for AD. Additionally, early diagnosis of these amyloid species can provide mechanistic understanding of protein aggregation and thus can pave the way for preventing the onset of AD. The aim of this...
Show moreProtein aggregation, oligomer and fibril formation is one of the dominant characteristics in the pathogenesis of a number of neurodegenerative diseases, such as Alzheimer’s disease (AD). Inhibition of toxic oligomer and fibril formation is one of the approaches to find potential drug candidates for AD. Additionally, early diagnosis of these amyloid species can provide mechanistic understanding of protein aggregation and thus can pave the way for preventing the onset of AD. The aim of this dissertation was 1) to explore the effects of charged cholesterol derivatives on the aggregation kinetic behavior of Amyloid-β40 (Aβ40), 2) to probe Aβ40 oligomer and amyloid formation in vitro using gold nanoparticles (AuNPs), and 3) to monitor the kinetic effect of various natural product molecules on Aβ40 aggregation in vitro. In the first chapter, a general introduction about AD as an amyloidogenic disease, amyloid cascade hypothesis, and the manipulation of Aβ peptides aggregation kinetics using different approaches was presented. In the second chapter, we studied the effects of oppositely charged cholesterol derivatives on the aggregation kinetics of Aβ. In the third chapter, we developed a gold nanoparticles (AuNPs) assay to probe Aβ40 oligomers and amyloid formation. In chapter IV, we monitored the effects of various small molecules on the aggregation kinetics of Aβ40. In chapter V, we discussed the methods and experimental details.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013009
- Subject Headings
- Alzheimer's disease, Amyloid beta-protein, Oligomers, Protein Aggregates, Neurodegenerative Diseases
- Format
- Document (PDF)
- Title
- Preserved and deficient calculation processes in Alzheimer's disease and mild cognitive impairment.
- Creator
- Jurado Noboa, Maria Beatriz., Charles E. Schmidt College of Science, Department of Psychology
- Abstract/Description
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Two skills necessary for the execution of proficient calculation, retrieving arithmetic facts from memory and accessing number magnitude information, were studied in a group of patients diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls to try to elucidate the locus of impairment in AD-related calculation deficits. This was achieved through the use of an arithmetic production task and a number-matching task as measures of explicit and implicit...
Show moreTwo skills necessary for the execution of proficient calculation, retrieving arithmetic facts from memory and accessing number magnitude information, were studied in a group of patients diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls to try to elucidate the locus of impairment in AD-related calculation deficits. This was achieved through the use of an arithmetic production task and a number-matching task as measures of explicit and implicit retrieval of arithmetic facts, and a numerical Stroop task that assesses automatic access to number magnitude representation. AD patients, but not MCI patients, showed high response latencies and a high number of errors when performing multiplications in the production task, and reduced automatic retrieval of arithmetic task in the number-matching task. All participants showed the classic problem-size effect often reported in the mathematical cognition literature. Performance on the numerical Stroop task suggests that access to number magnitude information is relatively resistant to cognitive impairment. ... Results for the AD group are consistent with a pattern of preserved and impaired cognitive processes that might mediate the reported calculation deficits in AD.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3362384
- Subject Headings
- Aging, Psychological aspects, Cognitive psychology, Memory disorders in old age, Alzheimer's disease, Diagnosis, Context effects (Psychology)
- Format
- Document (PDF)
- Title
- Aggregation kinetics of A\U+fffd\ peptides and the inhibition effects of small molecules on A\U+fffd\ peptide aggregation.
- Creator
- Hijazi, Ahmad Alex., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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The pathology of Alzheimer's disease (AD) remains elusive. Competing evidence links amylois \U+fffd\-peptide (A\U+fffd\) amyloid formation to the phenotype of AD (1). The mechanism of amyloid fibril formation has been an ongoing investigation for many years. A\U+fffd\10-23 peptide, a fragment of A\U+fffd\1-42 peptide, contained crucial hydrophobic core residues (2). In this study, an investigation was launched to study the aggreagation process of A\U+fffd\1023 peptide and its ability to form...
Show moreThe pathology of Alzheimer's disease (AD) remains elusive. Competing evidence links amylois \U+fffd\-peptide (A\U+fffd\) amyloid formation to the phenotype of AD (1). The mechanism of amyloid fibril formation has been an ongoing investigation for many years. A\U+fffd\10-23 peptide, a fragment of A\U+fffd\1-42 peptide, contained crucial hydrophobic core residues (2). In this study, an investigation was launched to study the aggreagation process of A\U+fffd\1023 peptide and its ability to form amyloid fibrils. Furthermore, the presence of its hydrophobic core showed importance for its ability to aggregate and form amyloid fibrils. Thereafter, the inhibition of A\U+fffd\1-42 peptide aggregation was studied by using pyrimidine-based compounds. A\U+fffd\1-42 peptides, known to be neurotoxic, aggregate to form amyloid fibrils (3). This investigation may provide insight into the development of novel small molecular candidates to treat AD.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3358550
- Subject Headings
- Amyloid beta-protein, Proteins, Metabolism, Disorders, Prions, Alzheimer's disease
- Format
- Document (PDF)
- Title
- Revisiting leisure activities and the risk of dementia in the elderly with special focus on dancing.
- Creator
- Stevens, Carrie., Charles E. Schmidt College of Science, Department of Mathematical Sciences
- Abstract/Description
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Data was provided by researchers of the Einstein Aging Study (EAS) of the Albert Einstein College of Medicine, Yeshiva University whom statistically analyzed data from the Bronx Aging Study cohort, concluding that participation in cognitive leisure activities and one physical activity, dancing, were associated with a reduced risk of dementia [1]. We explore data from a second (the EAS) cohort, utilizing Cox Proportional-Hazards and extended Cox regression [13]. Cognitive leisure activities in...
Show moreData was provided by researchers of the Einstein Aging Study (EAS) of the Albert Einstein College of Medicine, Yeshiva University whom statistically analyzed data from the Bronx Aging Study cohort, concluding that participation in cognitive leisure activities and one physical activity, dancing, were associated with a reduced risk of dementia [1]. We explore data from a second (the EAS) cohort, utilizing Cox Proportional-Hazards and extended Cox regression [13]. Cognitive leisure activities in general, and particularly doing crossword puzzles, reading books, watching television, and emailing are associated with a reduced risk of dementia. Doing aerobics, learning computer programming, babysitting, dancing, jogging singing, and weight training are associated with an increased risk of dementia. Participation in cognitive leisure activities in general, and reading books in particular, remains highly significant even after adjustment for well-known risk factors [14] such as: age, cognitive status, depression, medical illnesses, gender, ethnicity, education and economic status.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/FAU/3334097
- Subject Headings
- Aging, Psychological aspects, Older people, Health and hygiene, Forecasting, Older people, Mental health, Forecasting, Alzheimer's disease
- Format
- Document (PDF)
- Title
- Face processing in persons with and without Alzheimer's disease.
- Creator
- Winchester, Jeanna., Charles E. Schmidt College of Science, Center for Complex Systems and Brain Sciences
- Abstract/Description
-
This study aimed to understand the differences in strength or coordination of brain regions involved in processing faces in the presence of aging and/or progressing neuropathology (Alzheimer's disease). To this end, Experiment 1 evaluated age-related differences in basic face processing and the effects of familiarity in face processing. Overall, face processing in younger (22-35yrs) and older participants (63-83yrs) recruited a broadly distributed network of brain activity, but the...
Show moreThis study aimed to understand the differences in strength or coordination of brain regions involved in processing faces in the presence of aging and/or progressing neuropathology (Alzheimer's disease). To this end, Experiment 1 evaluated age-related differences in basic face processing and the effects of familiarity in face processing. Overall, face processing in younger (22-35yrs) and older participants (63-83yrs) recruited a broadly distributed network of brain activity, but the distribution of activity varied depending on the age of the individual. The younger population utilized regions of the occipitotemporal, medial frontal and posterior parietal cortices while the older population recruited a concentrated occipitotemporal network. The younger participants were also sensitive to the type of face presented, as Novel faces were associated with greater mean BOLD activity than either the Famous or Relatives faces. Interestingly, Relatives faces were associated with greater mean B OLD activity in more regions of the brain than found in any other analysis in Exp. 1, spanning the inferior frontal, medial temporal and inferior parietal cortices. In contrast, the older adults were not sensitive to the type of face presented, which could reflect a difference in cognitive strategies used by the older population when presented with this type of face stimuli. Experiment 2 evaluated face processing, familiarity in face processing and also emphasized the interactive roles autobiographical processing and memory recency play in processing familiar faces in mature adults (MA; 45-55yrs), older adults (OA; 70-92yrs) and patients suffering from Alzheimer's disease (AD; 70-92yrs)., MA participants had greater mean BOLD activity values in more regions of the brain than observed in either of the older adult populations, spanning regions of the medial frontal, medial temporal, inferior parietal and occipital cortices. OA, in contrast, utilized a concentrated frontal and medial temporal network and AD participants had the greatest deficit in BOLD activity overall.Age-related differences in processing faces, in processing the type of face presented, in autobiographical information processing and in processing the recency of a memory were noted, as well as differences due to the deleterious effects of AD.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/199330
- Subject Headings
- Face perception, Cognition, Age factors, Human face recognition, Alzheimer's disease, Facial expression, Physiological aspects
- Format
- Document (PDF)
- Title
- The use of novel HDACi's for treatment of memory impairment in a mouse model of Alzheimer's disease.
- Creator
- Moyes, Jonathan., Harriet L. Wilkes Honors College
- Abstract/Description
-
Alzheimer's disease (AD) is an increasingly common neurological disorder that mainly affects memory formation and retention. It is characterized by unique intercellular neurofibrillary tangles and extracellular beta-amyloid plaques. Histone deacetylase inhibitors (HDACi's) are competitive antagonists against histone deacetylases, causing histone acetyltransferases to acetylate the genome unregulated. This thesis investigates the use of new histone deacetylase inhibitors on recovering memory...
Show moreAlzheimer's disease (AD) is an increasingly common neurological disorder that mainly affects memory formation and retention. It is characterized by unique intercellular neurofibrillary tangles and extracellular beta-amyloid plaques. Histone deacetylase inhibitors (HDACi's) are competitive antagonists against histone deacetylases, causing histone acetyltransferases to acetylate the genome unregulated. This thesis investigates the use of new histone deacetylase inhibitors on recovering memory in a mouse model of Alzheimer's disease. By use of a fear conditioning paradigm, we have shown that these HDACI's increase memory in AD mice, but show either no effect or a positive effect in wild-type mice. Future experiments will investigate the efficacy of compound 966 and the spine density of hippocampal brain slices after fear conditioning trials.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3359315
- Subject Headings
- Alzheimer's disease, Chemotherapy, Pharmacogenetics, Histone deacetylase, Inhibitors, Nervous system, Degeneration, Molecular aspects
- Format
- Document (PDF)