Myelin – an untapped target for preventing or reversing brain aging

Myelin, traditionally thought of as the brain's electrical insulator, has emerged as an active and dynamic regulator of brain functions including neuroprotection, learning, and memory. Myelin dysfunction and loss is increasingly found to be central to brain aging and neurodegenerative diseases including Alzheimer's. However, the causes of myelin dysfunction and loss in the aged or diseased brain remain unknown, precluding therapies to promote its preservation and proper function. The research team is proposing three complementary aims that could each provide new insight into why myelin becomes dysfunctional in aging and disease, and how to reverse this. First, the team will build from recent discoveries in their lab to determine whether they can prevent myelin from becoming dysfunction in the aging brain. Second, they will build from another recent discovery in their lab that suggests myelin dynamics (as occurs during learning) predisposes myelin to degeneration. Last, the team will explore the role of an understudied myelin protein that has been linked to both extreme intelligence and Alzheimer's disease in humans. Together, this team's experiments have the potential to generate paradigm-shifting insights into the roles of myelin in promoting brain resilience, and unlock new therapeutic targets for preventing or reversing cognitive decline in aging and neurodegenerative disease.