Date of Award

Spring 2019

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Melissa A. Moss

Abstract

Despite the increasing prevalence of Alzheimer’s disease (AD), efforts to establish a definitive treatment or cure have met with little success. Many previous therapeutic strategies for AD have focused on the aggregation and accumulation of amyloid-b (Ab) in the brain, concentrating on its small intermediate aggregates as the primary targets to ameliorate neurotoxicity and damage. This approach has yielded little progress, and more recent discussions have shifted to strategies geared toward a multifaceted pathology, with chronic neuroinflammation emerging as an important factor in the disease etiology and progression.

The receptor for advanced glycation end-products, or RAGE, is a key pattern recognition receptor of the innate immune response that represents a broader and more integrated therapeutic target for both AD and chronic neuroinflammation. Observations that Ab is a ligand for RAGE implicate RAGE as a therapeutic target for AD, and RAGE has been proposed as a pathological vector in multiple inflammatory mechanisms associated with Ab. In addition, RAGE-mediated signaling is relevant in the progression of diseases that represent an increased risk in AD, such as Type II diabetes and cardiovascular disease, and RAGE potentiates and perpetuates chronic inflammation associated with aging. Because upregulation of transmembrane RAGE requires persistent inflammatory insult, quantifying levels of transmembrane RAGE expression is one avenue

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