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NIH Research Matters

NIH Research Matters

In This Edition

December 13, 2010

Insight into Memory Loss in Alzheimer’s Disease

A protein lost in Alzheimer’s disease may play a key role in memory development, according to a new study in mice. The findings give insight into how brain signals are disrupted by the disease and offer a potential new treatment target.

Microscope image showing clusters of red dots scattered among a field of green neurons.

NMDA receptors (red) in the mouse brain. Image courtesy of MRC Toxicology Unit, Wellcome Images. All rights reserved by Wellcome Images.

Alzheimer's disease leads to permanent losses in memory and other thinking skills, like learning and judgment. While its causes are still unclear, research has shown a strong relationship between the buildup of amyloid-beta proteins in the brain and damage to memory. How these proteins may contribute to memory loss, though, is largely unknown. Recent work has suggested that free-floating amyloids may play more of a role than the well-known amyloid plaques.

Past studies have reported that both Alzheimer's patients and mice with an Alzheimer's-like condition have lower levels of NMDA receptor activity, which is known to be involved in memory formation. Researchers have also found lower levels of the receptor tyrosine kinase EphB2, which is known to regulate NMDA levels.

A team of researchers led by Dr. Lennart Mucke from the Gladstone Institute of Neurological Disease in San Francisco decided to test how free-floating amyloids affect the levels of these molecules. They used both normal mice and transgenic mice that make high levels of human amyloid proteins. The transgenic mice have memory and neuron-signaling problems that resemble those in humans with Alzheimer's disease. They also have lower levels of EphB2 than normal mice. The study was supported by several grants from NIH.

In the November 28, 2010, issue of Nature, the team reported that free-floating amyloids bind to EphB2 and lead it to be broken down by the cell. When the researchers depleted EphB2 in cultured neuron cells from normal mice, they found that the loss of this protein led to less activity from NMDA receptors.

The team then tested how EphB2 levels affected memory formation in the mice. Depleting EphB2 from normal mice led to decreases in neuron signaling that mimicked those seen in the amyloid transgenic mice. When the scientists expressed high levels of EphB2 in the transgenic mice, they saw improvement in neuron signaling as well as in memory and learning tests.

These results suggest that Alzheimer's disease might someday be treated by modifying EphB2 levels or preventing its breakdown. "Based on our results, we think that blocking amyloid proteins from binding to EphB2 and enhancing EphB2 levels or function with drugs might be of benefit in Alzheimer's disease," Mucke says.

Although humans share many characteristics with mice, promising findings in animal models don’t always translate to humans. Nevertheless, this study represents a step forward in understanding how memory loss may occur in Alzheimer's disease, and hints at how that loss might be prevented or treated.

—Allison Bierly, Ph.D.

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About NIH Research Matters

Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

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This page last reviewed on December 3, 2012

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