Researchers Examine Plaque Formation Linked to Alzheimer’s Disease

Cleveland Clinic researchers are unravelling the mystery of how unique plaque accumulates in the brains of Alzheimer’s disease patients. The research could lead to new therapies for a disorder that affects an estimated 4 million Americans.

Research by Riqiang Yan, Ph.D., of Cleveland Clinic’s Lerner Research Institute, and his colleagues found that increased levels of the protein reticulon 3 (RTN3) causes the formation of dystrophic neuritis, which are abnormal or swollen nerve cell extensions that are a unique pathological feature of patients living with Alzheimer’s disease (AD).”For the first time, we have been able to link the presence of dystrophic neuritis to cognitive failure, and we show that over-expression of RTN3 early and under abnormal circumstances can cause neuritic abnormality seen in AD,” Yan said. “RTN3 isn’t just another protein trapped within dystrophic neuritis, but is actively involved in their formation.” Yan’s research shows that even a modest increase in RTN3 is sufficient to cause formation of dystrophic neuritis and even if that does not lead to Alzheimer’s disease there is still cognitive impairment. This study raises intriguing questions such as whether and how the presence of dystrophic neurites will impact the formation of amyloid deposition which is often associated with the onset of AD. The animal model generated in his laboratory will be useful to address this important question. “The research also suggests that suppressing RTN3 aggregation may not only delay dysfunction, but also inhibit enzymes that create plaques that are associated with Alzheimer’s disease,” Yan said. Dr. Yan was assisted by Xiangyou Hu, M.D., Ph.D., Qi Shi, M.D., Ph.D., Xiangdong Zhou, Ph.D., Wanxia He, and Xinghua Yin, M.D., of the Institute’s Department of Neurosciences; and Hong Yi, Marla Gearing, Ph.D., and Allan Levey, M.D., Ph.D., of the Emory University School of Medicine. (Source: EMBO Journal : Molly Johnson : Cleveland Clinic : September 2007)