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2008 Grants - Ohno
Testing of Rab5 - Overexpressing Mice as a Novel Alzheimer's Disease Model
Masuo Ohno, Ph.D.
The Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York
2008 Investigator-Initiated Research Grant
Amyloid precursor protein is the parent molecule of beta-amyloid, a key suspect in Alzheimer's disease. In healthy cells, APP is transported from one cellular compartment called the endosome to another compartment. When this transportation system breaks down, however, APP accumulates in the endosome and enlarges it. Lack of APP transport also results in elevated levels of beta-amyloid, and it may be a key factor contributing to the development of Alzheimer's.
Recent studies suggest that a protein called Rab5 may play a role in inhibiting proper APP transport. Furthermore, Rab5 activities may also damage synapses, the tiny channels through which brain cells send and receive chemical messages. Synaptic damage is a hallmark of Alzheimer's, and it leads to memory loss.
Masuo Ohno, Ph.D., and colleagues plan to learn more about how Rab5 might cause Alzheimer-related pathologies through both endosome enlargement and damage to synapses. For this effort, the researchers will develop a novel mouse model that overproduces Rab5 and APP. Dr. Ohno's team will test whether the mice experience increased levels of beta-amyloid and cell damage. The investigators will also administer cognitive tests to the mice to see if they suffer significant memory loss.
Results of this study could shed new light on how Alzheimer's disease develops at its earliest stages. Such knowledge could lead to improved methods of Alzheimer diagnosis and treatment.