Date of Award

2022

Document Type

Dissertation

Degree Name

Ph.D.

Department

Biological Sciences

First Advisor

Daniel A. Linseman

Second Advisor

Nancy Lorenzon

Third Advisor

David Patterson

Fourth Advisor

Yan Qin

Fifth Advisor

Charlotte Granholm-Bentley

Keywords

Alzheimer's, Pathology

Abstract

Alzheimer’s Disease is a multifarious disease that progressively affects more people as both the proportion of older adults in the population and life expectancy increase in both the United States and worldwide. This devastating disease is a result of rampant neuronal loss in the memory centers of the brain that robs the independence of those who are diagnosed and places a heavy burden on those who care for them. Traditionally speaking, research has focused on the hallmark pathology of amyloid plaques, targeting them to try and prevent disease onset. However, countless failures in clinical trials aimed at this said pathology has led researchers to broaden the horizon of what targets might be successful in mitigating disease. Additionally, the lack of a common cause in the majority of all cases, which are sporadic, demands a more dynamic approach to treating disease pathogenesis.

Thus, identifying alternative mechanisms and ways to prevent them during disease development is vital to help design new therapeutic interventions beyond amyloid alone. Presented here are a collection of mechanisms uncovered that likely play into the development of Alzheimer’s Disease and pose potential new routes for therapies to improve patient outcomes. Here we propose two pharmacological interventions including that of inhibiting polyamine synthesis to reduce amyloid aggregation and toxicity as well as preventing the production of the APP intracellular domain due to its neurotoxic role at the mitochondria. Additionally, we offer a nutritional intervention through the antioxidative and amyloid preventive effects of a cysteine-rich Whey protein, Immunocal®. Lastly, we introduce the Kynemics program at the Alumia Institute, a lifestyle intervention which utilizes a multi-modal immersive approach to improve patient measures and reduce the burden on their caregivers. Overall, future interventions designed to address Alzheimer’s Disease should reflect the fact that it is a complicated disease; thus, generating the treatments that will be most successful will likely require the targeting of multiple pathways to prevent or slow disease pathogenesis and in turn improve patient well-being and overall societal burden.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Provenance

Received from ProQuest

Rights holder

Alexandra A. Sandberg

File size

242 pgs

File format

application/pdf

Language

en

Discipline

Molecular biology, Neurosciences, Cellular biology

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