Novel Amyloid-beta Clearance Mechanisms at the Blood-Brain Barrier
Detailed Non-Technical Summary
The primary goal of this research project is to develop a greater understanding of the integrity of blood vessels in the brain in the context of Alzheimer's disease. In addition, we hope to develop a novel form of therapy aimed at removing the toxic amyloid-beta peptide from the brains of individuals with Alzheimer's disease.
The brain is an energy-demanding tissue requiring nutriment and oxygen, while at the same time needing protection from other potentially harmful agents, for example, viral or bacterial particles which may be delivered by the circulation. For this reason, cells lining the walls of the fine capillaries that supply blood to the brain have tight junctions, which, as the name implies, reduce the space between these cells essentially to zero, forming an exceedingly tight seal. This barrier is termed the blood-brain barrier (BBB) and it performs the essential role of preventing the majority of blood-borne components from gaining access to delicate neural tissues. Here, we will examine how amyloid beta, a peptide that has previously been found to accumulate in the brains of Alzheimer's disease patients, can exert an impact on the tight junctions and how we may be able to facilitate greater clearance of amyloid-beta from brain blood using a technology termed RNA-interference combined with current antibody-based developmental drugs.
We believe our project focuses on an area of Alzheimer's disease pathology that has remained largely unexplored to date. In addition, the findings associated with this project have the potential to lead to a novel form of combination therapy for Alzheimer's disease that could offer hope to patients and carers alike.
Once this study is completed, we hope to be in a position where we will have a more profound understanding of the "dysfunctional" BBB in Alzheimer's disease. Added to this, we envision the development of a new form of therapy that could have multiple benefits in the clinical management of Alzheimer's disease.
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