Massachusetts General Hospital
Massachusetts General Hospital
Blood-Brain Barrier Imaging in Mild Cognitive Impairment and Alzheimer Disease
Given the questionable effectiveness Aduhelm on clinical outcomes, there is a need to identify other potential causes and therapeutic targets for Alzheimer disease (AD). A promising area of further investigation is blood-brain barrier (BBB) dysfunction. The BBB is a structure that protects the brain from neurotoxins that may be circulating in the blood. It is also an important feature of the brain’s waste disposal mechanism, the glymphatic system. There is evidence the water flow across the BBB and glymphatic flow decreases as we age, making the brain vulnerable buildup of potentially harmful substances. We have developed an MRI method that can measure water flow across the BBB without the need of intravenous contrast. In our preliminary study, we were able to show that BBB water flow was lower in older subjects relative to younger subjects. Our objective for the proposed study is to evaluate water flow cognitively normal subjects as well as participants with AD and mild cognitive impairment. If BBB dysfunction precedes and directly contributes to AD pathogenesis, BBB water flow could be a viable measure in AD clinical trials for therapies targeting the BBB or glymphatic system.