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Editor's e-Note
A study in mice published in Nature indicates that when the function of the lymphatic system in the brain is enhanced, the ability to reduce the buildup of amyloid-beta is increased. Researchers found that treatment of mice with monoclonal antibodies was less effective in mice with a less functional lymphatic system.

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— Kate Jackson, editor
e-News Exclusive
A ‘Lymphatic Boost’ May Improve Outcomes in Alzheimer’s Disease

Enhancing the brain’s lymphatic system when administering immunotherapies may lead to better clinical outcomes for Alzheimer’s disease patients, according to a new study in mice. Results recently published in Nature suggest that treatments such as the immunotherapies BAN2401 or aducanumab might be more effective when the brain’s lymphatic system can better drain the amyloid-beta protein that accumulates in the brains of those living with Alzheimer’s.

“A broad range of research on immunotherapies in development to treat Alzheimer’s by targeting amyloid-beta has not to date demonstrated consistent results,” says Richard J. Hodes, MD, director of the National Institute on Aging (NIA). “While this study’s findings require further confirmation, the link it has identified between a well-functioning lymphatic system in the brain and the ability to reduce amyloid-beta accumulation may be a significant step forward in pursuing this class of therapeutics.”

Abnormal buildup of amyloid-beta is one hallmark of Alzheimer’s disease. The brain’s lymphatic drainage system, which removes cellular debris and other waste, plays an important part in that accumulation.

A 2018 NIA-supported study showed a link between impaired lymphatic vessels and increased amyloid-beta deposits in the brains of aging mice, suggesting these vessels could play a role in age-related cognitive decline and Alzheimer’s. The lymphatic system is made up of vessels that run alongside blood vessels and carry immune cells and waste to lymph nodes. Lymphatic vessels extend into the brain’s meninges, which are membranes that surround the brain and spinal cord.

For this new study, the research team sought to determine whether changing how well the lymphatic drainage works in the brain could affect the levels of amyloid-beta and the success of antibody treatments that target amyloid-beta. Using a mouse model of early-onset Alzheimer’s, researchers removed some of the lymphatic vessels in the brains of one group of mice. They treated these mice, as well as a control group, with injections of monoclonal antibody therapies, including a mouse version of aducanumab.

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