Novel Approaches to Evaluate the Amyloid Cascade Hypothesis
This talk will describe a multidisciplinary approach by the integration of medicinal chemistry with molecular imaging and drug delivery to re-assess the role of amyloid in Alzheimer’s disease (AD). Particularly, the investigation of the role of oxidative stress in the initiation of amyloid aggregation will be discussed. The brain is more vulnerable than any other organs to oxidative stress given major components of the neurons, such as lipids, proteins and nucleic acids can be oxidized in AD that leads to increased inflammation and amyloid aggregation. If this mechanism is proven to be accurate, routine consumption of antioxidant-rich diets could be used for the prevention of AD. While, our study also suggests that the development of biologic-based treatment of AD should take blood-brain barrier (BBB) into consideration, which is a formidable barrier that blocks most of the large molecules from penetrating the brain parenchyma unless the delivery is facilitated by receptor-mediated mechanisms. Alternatively, delivery to the brain bypassing the BBB via the olfactory epithelium can be achieved by atomizing the drug formulation for nebulization. This route of distribution is ideal for AD since the materials would end up in the subiculum before diffusing to the hippocampal region. During this presentation, I will also discuss the development of methods for imaging amyloid deposit in the retina for early detection of AD. Notably, optical imaging of the ocular amyloidal deposit is much easier, economical, and faster compared to imaging the same material deep inside in the brain.