Emory University scientists are using a combination of transgenic mouse models and viral vectors to clarify the role of a brain molecule called LR11 in Alzheimer's disease (AD). LR11 is a receptor for apolipoprotein E, which is involved in cholesterol metabolism and has previously been linked to AD. Early studies suggest that LR11 regulates levels of beta amyloid, which is the primary protein comprising the senile plaques in the brains of Alzheimer's patients.
Sara E. Dodson, BS, a neuroscience program graduate student in Emory University's Division of Biological and Biomedical Sciences, presented results of her team's research at the 9th International Conference of Alzheimer's Disease and Related Disorders in Philadelphia on July 20.
The Emory scientists already have used human brain tissue to show that LR11 is markedly reduced in patients with Alzheimer's disease. In their current experiments, they combined special viruses, called lentiviruses, to selectively reduce and enhance LR11 expression in mouse brains and cultured cells to study the function of LR11.
Lentiviruses are special in their ability to infect neurons and permanently alter expression of certain genes by the infected cells. The Emory scientists successfully used these viruses to deliver artificial genes into neurons to control expression of LR11 in mouse brains. When this approach was used in cultured cells to reduce LR11 levels and mimic the situation in Alzheimer's brains, there was a marked increase in beta amyloid, suggesting that LR11 plays a key role in regulating levels of this important molecule.
"The combination of transgenic mouse models and viral vectors appears to be a powerful tool to evaluate the role of LR11 in the accumulation of beta amyloid and the development and progression of Alzheimer's disease," according to Ms. Dodson. "We are continuing to develop more detailed and specific viral vector constructs to study the results of overexpression and underexpression of LR11."
Other members of the Emory neurology research team include Principal Investigators James J. Lah and Allan I. Levey, Katrin Offe, James T. Shoemaker, Kristen Sager, Stephanie C. Carter, Guofu Fang, and Xinping Huang.