A protein called midkine may help prevent brain plaques that contribute to Alzheimer’s disease, reports a new study by St. Jude Children’s Research Hospital, Van Andel Institute and collaborators.
The findings give scientists a new avenue for pursuing therapies designed to slow or stop disease development and progression by targeting a key hallmark of Alzheimer’s.
“One of the biggest problems in Alzheimer’s treatment is that still we don’t have an effective way to prevent or clear out these harmful plaques,” said Yang Yang, Ph.D., an assistant professor at VAI and co-corresponding author of the study. “Our research shows that the presence of midkines interferes with the formation of plaques. Although we’re still in the early stages, I’m hopeful that our work will help inform new treatment strategies that address one of the root issues in Alzheimer’s.”
Plaques are formed by a buildup of amyloid-beta proteins in the brain, which stick together and create sheets that disrupt cellular communication and contribute to cell death. As the plaques worsen and cause more damage, people with Alzheimer’s experience memory loss and other symptoms.
The new findings, published in Nature Structural & Molecular Biology, suggest that midkine is found in the brain alongside amyloid-beta. Rather than causing damage, however, midkine prevents amyloid-beta from aggregating into plaques. The research team, led by Yang, St. Jude’s Junmin Peng, Ph.D., and St. Jude’s Ping-Chung Chen, Ph.D., used several different techniques to demonstrate and confirm that the presence of midkine reduces plaque formation.
They also found that “silencing” the gene that contains the instructions for midkine led to significant increases in amyloid-beta plaques.
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Yang and her team contributed to the findings by using advanced modeling tools to investigate interactions between midkine and amyloid-beta. In the future, she plans to leverage VAI’s high-powered cryo-electron microscopy suite to study this important interaction in deeper detail.
“Revealing how these proteins interact gives us a foundation for developing potential medications that mimic midkine’s ability to prevent plaques,” Yang said. “I’m excited to see where this research takes us.”
Yang is supported by Van Andel Institute.
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award nos. R01AG053987 (Peng), RF1AG064909 (Peng and Yu), RF1AG068581 (Peng and Rossoll), U19AG069701 (Asmann), P30AG019610 (Alexander) and P30AG072980 (Alexander); the National Cancer Institute of the National Institutes of Health under award no. P30CA021765 (Akers); the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award no. U24NS072026 (Beach); the Arizona Department of Health Services; the Arizona Biomedical Research Commission; the Michael J. Fox Foundation for Parkinson’s Research; and the American Lebanese Syrian Associated Charities (ALSAC), the fundraising and awareness organization of St. Jude. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders.
Image caption: A new study from St. Jude Children’s Research Hospital, Van Andel Institute and collaborators suggests that the protein midkine (in red) helps prevent amyloid-beta proteins (in green) from forming Alzheimer’s disease-associated plaques.