How APOE4 causes neuro problems

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APOE4-

Biochemical Pathway by Which Harmful Molecule May Raise Alzheimer's Risk

From HealthNewsDigest.com Jun 14, 2010

The researchers looked at receptors that respond to a neurotransmitter called

glutamate, which is implicated in memory and learning. In mice that were

genetically altered to make human APOE4, the researchers found that APOE4

prevented the cells from accomplishing a vital step in learning – becoming

more sensitive to repeated signals.

Dr. Herz and his colleagues hypothesized that APOE4 exerted its effects by

interacting with the receptors for a molecule called Reelin, which keeps brain

cells more sensitive to each other. Both APOE4 and Reelin bind to the same

receptor. When Reelin binds to it, the combination triggers a biochemical

cascade that makes the glutamate receptor more sensitive to incoming signals.

The researchers showed that APOE4 prevents the Reelin-binding receptor from

being recycled back to the surface. With fewer receptors, the nerve cell can’t

bind much Reelin, no matter how much is around. Without Reelin’s effects, the

cell doesn’t respond as vigorously to glutamate, and doesn’t “learn†as

well.

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