Medicine and Health Sciences Commons^™

Mri Investigations Of Metabolic And Structural Brain Changes In Alzheimer’S Disease And Vitamin D Deprivation, Dickson Wong

Electronic Thesis and Dissertation Repository

Alzheimer's disease (AD) is a neurodegenerative disorder of the brain that presents as progressive impairment across several cognitive domains. The biological mechanisms underlying the development of AD remain unclear, with amyloid-beta plaques, neurofibrillary tangles, calcium dysregulation, and oxidative stress all contributing to neurodegeneration in AD. Vitamin D (VitD) deficiency, a common condition in the elderly, may modulate these mechanisms and complicate the AD process. Due to this complicated pathogenesis, the diagnosis of AD requires subjective clinical judgement, staging of AD is challenging, and it remains difficult to predict when and who will progress to AD. The purpose of this thesis …

Using Genetic Diversity To Understand Susceptibility To Cognitive Decline In Aging And Alzheimer’S Disease, Sarah M. Neuner

Theses and Dissertations (ETD)

An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging and transition to dementia such as Alzheimer's disease (AD). Identifying the specific genetic variants that contribute to cognitive aging and AD may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we turned to genetically diverse mice from the BXD genetic reference panel (GRP) to overcome some of the …

Pathological Tau As A Cause, And Consequence, Of Cellular Dysfunction, Shelby Meier

Theses and Dissertations--Physiology

Tauopathies are a group of neurodegenerative diseases characterized by the abnormal deposition of the protein tau, a microtubule stabilizing protein. Under normal physiological conditions tau is a highly soluble protein that is not prone to aggregation. In disease states alterations to tau lead to enhanced fibril formation and aggregation, eventually forming neurofibrillary tangles (NFTs). The exact cause for NFT deposition is unknown, but increased post-translational modifications and mutations to the tau gene can increase tangle formation.

Tauopathic brains are stuck in a detrimental cycle, with cellular dysfunction contributing to the development of tau pathology and the development of tau pathology …