Neuronal receptor response may help explain Alzheimer's memory loss

Based on laboratory research, scientists at Georgetown University Medical Center have a new theory as to why people with Alzheimer's disease have trouble performing even the simplest memory tasks, such as remembering a family member's name.

That's because they discovered a physical link between apolipoprotein E (APOE), the transport molecules known to play a role in development of the disease, and glutamate, a brain chemical necessary for establishing human memory.

In a study published in the Journal of Biological Chemistry, the research team specifically found that receptors on the outside of brain nerve cells (neurons) that bind on to APOE and glutamate are connected on the surface of neurons, separated from each other by only a small protein.

While the researchers don't know why these receptors are linked together, they say inefficient or higher-than-average levels of APOE in the brain could possibly be clogging these binding sites, preventing glutamate from activating the processes necessary to form memories.

"We have found out that two receptors previously thought to have nothing to do with each other do, in fact, interact, leading us to conclude that APOE affects the NMDA glutamate channel that is important in memory," says the study's senior author, G. William Rebeck, PhD, associate professor of neuroscience in Georgetown's Biomedical Graduate Research Organization.

The researchers also hypothesize that this interaction might have something to do with development of Alzheimer's disease, although they stress that at this early stage of research, this is impossible to prove.

Rebeck and first author Hyang-Sook Hoe, PhD, also of Georgetown, say that laboratory work now underway is attempting to unravel the relationship between APOE and NMDA receptors.

APOE is a protein that helps shuttle cholesterol and other non-soluble lipid particles around the body, moving these substances to where they are needed.

Contact: Liz McDonald
Georgetown University Medical Center

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