Assessing the Impact of Blood Brain Barrier Dysfunction on CSF Tau Levels in Alzheimer’s Disease

The goal of the project is to identify novel biomarkers and key targets for BBB breakdown and explore how it may contribute to Alzheimer’s Disease diagnosis and progression.

Blood brain barrier (BBB) breakdown has been observed in various neurodegenerative diseases including Alzheimer’s disease. In a healthy brain, the BBB does not allow transportation of proteins or large molecules into the brain. However, due to BBB dysfunction, enhanced permeability of plasma derived proteins can be observed in different parts of brain regions, and has been proposed to lead to neurotoxicity, neuroinflammation, and oxidative stress. This project will identify novel biomarkers and key targets for BBB breakdown and explore how it may contributes to AD diagnosis and progression.

1. Deep and comprehensive network driven proteomics by unbiased subtyping will help to resolve molecular heterogeneity across different patient demographics in the Alzheimer’s disease progression.

2. BBB damage has been reported due to aging. However, relation between various proteolytic enzymes such thrombin and MMPs and reduced tau level in CSF in association with BBB damage is yet to be understood. This study will provide novel insights about various proteolytic enzymatic cleavage sites for tau reduction and its role in BBB damage.

This project will identify novel biomarkers for BBB breakdown and its association to Alzheimer’s disease diagnosis and progression.