Mechanisms of plasma proteins that rejuvenate the aged brain

One in three people will develop Alzheimer’s disease or another dementia during their lifetime, but effective treatment still does not exist despite intense efforts. Recently, blood from young mice has been found to rejuvenate several tissues of old mice, including the brain. By using transfusions of young blood, we may be able counteract the cognitive decline seen in Alzheimer’s disease through restoration of learning and memory. Proteins in blood plasma appear to mediate the rejuvenative effect, but where these proteins are produced in the body and how they cause these effects in the brain is unknown, both important questions for developing suitable therapies. To address these questions, I am devising a method to label proteins from a specific tissue or organ, for example the liver, to distinguish them after they are secreted into the complex mixture of proteins in blood plasma. I can then track these proteins to uncover the final target in the brain that may lead to restored learning and memory of an old mouse. The blood-brain barrier prevents most molecules in blood from entering brain tissue, so I will determine if proteins enriched in young blood can either directly enter the brain or indirectly signal through nearby blood vessels. I can also determine which cell types in the brain are affected and begin to uncover which protein receptors are targeted. This study will potentially lead to more effective and targeted treatments for Alzheimer’s disease and introduce useful tools for the study of proteins in blood that can affect the health of many tissues.