Memory Problems in Mice with Alzheimer's Treated by New Gene Therapy

A new gene therapy that was successful in treating memory problems in mice with Alzheimer's disease (AD)was discovered by scientists. The study was done at the Gladstone Institute of Neurological Disease in San Francisco.

Learning and memory requires 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.

"EphB2 is a really cool molecule that acts as both a receptor and an enzyme. 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," said Moustapha Cisse.

Reducing EphB2 levels in normal healthy mice disrupted neurotransmission and gave them memory problems similar to those seen in AD.

"What we were most curious about, of course, was whether normalizing EphB2 levels could fix memory problems caused by amyloid proteins. We were absolutely thrilled to discover that it did," said Lennart Mucke, director of the GIND.

Increasing EphB2 levels in neurons of mice engineered to produce high levels of human amyloid proteins in the brain prevented their neurotransmission deficits, memory problems and behavioral abnormalities.

The scientists also discovered that amyloid proteins directly bind to EphB2 and cause its degradation, which helps explain why EphB2 levels are reduced in AD and related mouse models.

"We are excited about these possibilities and look forward to pursuing them in future studies," said Mucke.

The findings will be published in the November 28 issue of the journal Nature.

Source: ANI