New OHSU research suggests possible target in fight against Alzheimer’s

Two images compare brain scans from an older individual who had Alzheimer's (left) with an older cognitively healthy individual (right).

Two images compare brain scans from an older individual who had Alzheimer’s (left) with an older cognitively healthy individual (right).

In most of the human body, the lymphatic system clears away waste and toxins. The brain, however, has no lymphatic vessels. Its waste, including plaques associated with Alzheimer’s disease, is cleaned instead by cerebrospinal fluid recirculating through brain tissue. Over the course of five years, research in the lab of Jeffrey Iliff, Ph.D., has defined this brain-wide paravascular pathway, called the glymphatic system.

Iliff’s team has found that this recirculation is modulated by sleep and also that, as the brain ages, this waste-clearing process is impaired. Their work continues to investigate what causes the glymphatic system to slow. In research findings published November 28 in the journal JAMA Neurology, Iliff demonstrates the possible role of aquaporin-4, a membrane protein in the brain and key component of the glymphatic system.

The study examined 79 brains donated through the Oregon Brain Bank, a part of the OHSU Layton Aging and Alzheimer’s Disease Center. Researchers found that in the brains of younger people and older people without Alzheimer’s, the aquaporin-4 protein was well organized, lining the blood vessels of the brain. However, within the brains of people with Alzheimer’s, the aquaporin-4 protein appeared disorganized, which may reflect an inability of these brains to efficiently clear away wastes like amyloid beta.

The study suggests that future research focusing on aquaporin-4 might find it to be a useful target for potentially preventing and treating Alzheimer’s disease.

In addition to Iliff, co-authors included Douglas M. Zeppenfeld; Matthew Simon, J. Douglas Haswell, and Daryl D’Abreo of the OHSU Department of Anesthesiology and Perioperative Medicine. See the paper for a full list of authors.

This work was supported by funding from the American Heart Association, grant 12SDG11820014, the Oregon Partnership for Alzheimer’s Research, grants from the Research and Development Office of the Department of Veterans Affairs and the National Institutes of Health (NS089709), including Alzheimer’s Disease Center grant AG08017 from the National Institute on Aging that supported the longitudinal follow-up and subsequent brain autopsies providing the human brain samples used in this study.

Read the full OHSU news release.

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About the Author

Casey Williamson writes about research at OHSU.

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