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Gene therapy prevents memory problems in mice with Alzheimer's disease
Date:11/28/2010

SAN FRANCISCO, CANovember 21, 2010 Scientists at the Gladstone Institute of Neurological Disease (GIND) in San Francisco have discovered a new strategy to prevent memory deficits in a mouse model of Alzheimer's disease (AD). Humans with AD and mice genetically engineered to simulate the disease have abnormally low levels of an enzyme called EphB2 in memory centers of the brain. Improving EphB2 levels in such mice by gene therapy completely fixed their memory problems. The findings will be published in the November 28 issue of the journal Nature.

In both humans and mice, learning and memory requires effective communication between brain cells called neurons. This communication involves the release of chemicals from neurons that stimulate cell surface receptors on other neurons. This important process, called neurotransmission, is impaired by amyloid proteins, which build up to abnormally high levels in brains of AD patients and are widely thought to cause the disease. But how exactly these poisonous proteins disrupt neurotransmission is unknown.

"EphB2 is a really cool molecule that acts as both a receptor and an enzyme," said Moustapha Cisse, PhD, lead author of the study. "We thought it might be involved in memory problems of AD because it is a master regulator of neurotransmission and its brain levels are decreased in the disease."

To determine if low EphB2 levels actually contribute to the development of memory problems, the investigators used gene therapy to experimentally alter EphB2 levels in memory centers of mice. Reducing EphB2 levels in normal healthy mice disrupted neurotransmission and gave them memory problems similar to those seen in AD. This finding suggests that the reduced EphB2 levels in AD brains contribute to the memory problems that characterize this condition.

"What we were most curious about, of course, was whether normalizing EphB2 levels could fix memory problems caused by amyloid proteins
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Contact: Gary Howard
ghoward@gladstone.ucsf.edu
415-734-2044
Gladstone Institutes
Source:Eurekalert

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