UM Scientists Delay Plaque Growth In Alzheimer's Disease

Researchers from the University of Michigan (UM) discovered a molecular process that could be used to potentially delay development of Alzheimer’s disease in patients. The team’s findings will appear in an upcoming edition of the Proceedings of the National Academy of Sciences.

It has been observed that a cellular structure called the Golgi becomes fragmented in all patients with Alzheimer’s disease (AD). The fragmentation is thought to be one of the major causes of the disease, though no one knows the exact cause. The UM researchers said that understanding the mechanism is crucial to decoding amyloid plaque formation in the brain tissue of patients with AD. Amyloid plaque formation is a trademark in AD and causes memory loss and other symptoms. The team studied the molecular process behind Golgi fragmentation and also developed two techniques to rescue the cellular structure.

Yanzhuang Wang, UM associate professor of molecular, cellular and developmental biology, said, “We plan to use this as a strategy to delay the disease development. We have a better understanding of why plaque forms fast in Alzheimer's and found a way to slow down plaque formation.”

The Golgi structure is considered to play an important role of sending molecules to the right places to facilitate proper function of cells, Wang said. Fragmentation leads to disorganized or even failed distribution of the molecules. The team found that accumulation of the abeta peptide, which drives plaque formation in the brain, triggers the fragmentation of the Glogi structure through activation of an enzyme called cdk5. The enzyme modifies Golgi structural proteins such as GRASP65.

Wang and his team rescued the Golgi structure by either inhibiting cdk5 or by expressing a mutant of GRASP65 that cannot be modified by cdk5. Both strategies decreased abeta peptide secretion by about 80%.

The team said it plans to study the treatment strategy in mice under a collaboration with the Michigan Alzheimer's Disease Center at the UM Health System.