For decades, Alzheimer’s research has focused heavily on the toxic protein plaques that build up in the brain. However, emerging evidence suggests that the chain reaction leading to Alzheimer’s disease may begin with microvascular failure – the breakdown of the brain’s smallest blood vessels—before substantial protein accumulation.
Led by Lee, a new research project aims to transform how we understand and treat Late-Onset Alzheimer’s Disease (LOAD). Preliminary results suggest that female lab mice carrying the human Alzheimer’s risk gene APOE4 may lose critical ‘back-up routes’ in the brain’s smallest blood-vessel networks, potentially making them more vulnerable to tiny disruptions in blood flow. These microscopic failures happen long before observable memory or cognitive decline occurs.
To catch and reverse this damage early, Lee and team are building an open-source platform combining advanced optical imaging and artificial intelligence. The project will map early blood flow changes, by tracking how brain vessel networks fail over time using high-speed, label-free optical imaging; investigate how genetic risk factors may disrupt vital communication signals within blood vessel walls; and evaluate in mouse models whether combining existing vascular drugs (such as statins) with current Alzheimer’s therapies can rescue blood flow and protect long-term brain health.
By catching Alzheimer's at an early vascular stage, this research hopes to unlock new therapeutic targets and buy crucial time for millions at risk.