Medicine and Health Sciences Commons^™

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is unknown. Recent studies have implicated alterations in calcium homeostasis as a pathogenic contributor to AD. Calcium dysregulation has been observed in aged and AD brains, an event which could potentially facilitate the development of multiple pathologies observed in AD. Specifically, disrupting intracellular calcium levels in vitro has been demonstrated to increase amyloid-beta (Aβ) production, tau phosphorylation, and neuronal loss. However, there is a paucity of data on the behavioral and biochemical consequences of chronic in vivo perturbation of calcium homeostasis. In a series of experiments designed to evaluate the …

An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn

Electronic Thesis and Dissertation Repository

Identifying mechanisms underlying the synergistic pathological interaction between stroke and Alzheimer’s disease (AD) can effectively guide future therapeutic strategies for these highly co-morbid conditions. Aberrant ganglioside expression marked by the pathological accumulation of ganglioside GM3 is common to stroke and AD, yet it is unclear whether GM3 is synergistically enhanced in a comorbid model, or if GM3 is a viable therapeutic target. Adult male Wistar rats received a unilateral ischemic striatal infarct via endothelin-1 (ET-1) injection alone or in combination with bilateral intracerebroventricular injection of the β-Amyloid 25-35 peptide (Aβ) to induce generalized Aβ toxicity (Aβ/ET-1). Animals were sacrificed after …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Site-Directed Mutations In The C-Terminal Extension Of Human Αb-Crystallin Affect Chaperone Function And Block Amyloid Fibril Formation, T. M. Treweek, Heath Ecroyd, D. M. Williams, S. Meehan, J. A. Carver, M. J. Walker

Heath Ecroyd

Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including αBcrystallin, play a role in the prevention of protein deposition. A series of site-directed mutants of the human molecular chaperone, αB-crystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of αB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal …

Glycemic Load And Risk Of Alzheimer's Disease: The Cache County Study On Memory, Health, And Aging, Eun Young Choi

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Carbohydrates are a major energy source for the human body and particularly glucose is the only energy source for the brain. Thus glucose metabolism is important to maintain normal brain function. Evidence showed insulin resistance and diabetes are associated with cognitive decline and a large amount of highly processed carbohydrate intake; in other words, a high glycemic load diet, which increases blood glucose faster and insulin demand, is associated with increased risk of insulin resistance and diabetes.

Based on this premise, the hypothesis that a high glycemic load (GL) diet increases the risk of incident Alzheimer’s disease (AD) was examined …

Site-Directed Mutations In The C-Terminal Extension Of Human Αb-Crystallin Affect Chaperone Function And Block Amyloid Fibril Formation, T. M. Treweek, Heath Ecroyd, D. M. Williams, S. Meehan, J. A. Carver, M. J. Walker

Faculty of Health and Behavioural Sciences - Papers (Archive)

Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including αBcrystallin, play a role in the prevention of protein deposition. A series of site-directed mutants of the human molecular chaperone, αB-crystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of αB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal …

The Effect Of Ginkgo Biloba On Alzheimer's Disease, Allison Marie Wozney

Undergraduate Honors Capstone Projects

Alzheimer's disease is a progressive dementia associated with increasing loss of memory, intellectual function, and disturbances in speech. It is the most common form of dementia. It is an incurable disease and has four stages which culminate in coma and death. The average survival rate for Alzheimer's is seven years. Presently, the only treatments approved in the United States for Alzheimer's are the drugs tacrine and donepezil. These drugs improve cognitive function in early Alzheimer's. However, Ginkgo biloba has recently been looked at as another treatment option and has been approved for use in Germany. Ginkgo Biloba was originally used …

Identification And Characterization Of Mitochondrial Dna Variants In Alzheimer's Disease, Natasha Singh Hamblet

Theses and Dissertations in Biomedical Sciences

Alzheimer's Disease (AD) is a complex neurodegenerative disorder that affects a significant portion of the human population regardless of ethnicity or gender. A mitochondrial hypothesis of AD has been proposed based on a number of studies which establish altered oxidative phosphorylation (OXPHOS) and ATP synthesis in AD tissue. ATP demand is most prevalent in the brain; damage to OXPHOS could severely impair brain metabolism, thereby leading to a decline in cognitive function. Four out of five complexes in the OXPHOS pathway are partly encoded by mitochondrial DNA (mtDNA); thus, this may be a crucial site of lesions that alter brain …