Despite evidence demonstrating that impairments in the clearance of toxic waste in the brain contribute to late-onset Alzheimer’s disease, the science of lymphatic system dysfunction and the systems regulating entry and exit through the blood-brain barrier has been largely overlooked in Alzheimer’s disease — until now. The Maxine and Richard Berg Brain Entry & Exit Consortium bring together an international team of scientists to consider the following question: how do different barriers within the brain communicate?
The recent discovery of lymphatic vessels in the brain has raised important questions. How are fluids, such as cerebrospinal fluid and various molecules, exchanged between different parts of the brain? How are toxic waste and other byproducts cleared from the brain? It took more than 200 years and the application of cutting-edge imaging techniques for the observation in the 18th century by Paoli Mascagni to be confirmed: the membranes that line the skull and enclose the brain and spinal cord contain lymphatic vessels that drain fluids from the brain.
The brain is comprised of multiple barriers including the blood-brain barrier, the blood-choroid plexus barrier, meningeal lymphatics, and the blood-meningeal barrier. The meningeal lymphatic vessels carry waste from the cerebrospinal fluids (CSF) to the lymph nodes and facilitate the removal of byproducts from the brain. While it is known that the brain recirculates the CSF, the details for how this process might change during aging, and the role of CSF and recirculation in neurodegeneration, requires more investigation. The CSF also regulates intracranial pressure, removal of waste such as amyloid-beta, and neuroinflammation. A decrease in CSF production and clearance is thought to contribute to the dysregulation in the brain that arises with aging and neurodegenerative diseases.
With grants from Cure Alzheimer’s Fund, these investigators are embarking on research that will determine how dysfunction in one of the brain barriers might impact others. And, since many drugs and antibodies do not make it to the brain because they are blocked by the blood-brain barrier, this research is critical for designing better systems of drug delivery.
The members of the Maxine and Richard Berg Brain Entry & Exit Consortium includes:
JONATHAN KIPNIS, PH.D., WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS, CHAIR OF THE CONSORTIUM
FERNANDA MARQUES, PH.D., UNIVERSITY OF MINHO SCHOOL OF MEDICINE
RICHARD DANEMAN, PH.D., UNIVERSITY OF CALIFORNIA, SAN DIEGO
ALI ERTURK, PH.D., HELMHOLTZ MUNICH
FANNY HERISSON, M.D., PH.D., HARVARD MEDICAL SCHOOL / MASSACHUSETTS GENERAL HOSPITAL
SE HOON CHOI, PH.D., HARVARD MEDICAL SCHOOL/MASSACHUSETTS GENERAL HOSPITAL, and ROGER KAMM, PH.D., MASSACHUSETTS INSTITUTE OF TECHNOLOGY