July 20, 2024
Modified protein can prevent Alzheimer's disease in mice
Neurons in the brain of a mouse with Alzheimer's disease. New research from UChicago shows how a modified piece of one protein can prevent the disease in mice.
Neurons in the brain of a mouse with Alzheimer’s disease. New research from UChicago shows how a modified piece of one protein can prevent the disease in mice.

The amyloid precursor protein has always been vilified as a major cause of Alzheimer’s disease. One of its fragments, the amyloid-beta peptide, can break off and accumulate in the brain, giving rise to the puffy white globs known as senile plaques that are a hallmark of the disease.

In a study published recently in the journal Cell Reports, however, researchers at the University of Chicago have redeemed APP as an unlikely hero, uncovering its extended role in brain signaling that can prevent the development of Alzheimer’s disease in mice.

So, when does APP take on the mantle of hero versus swooping in as the villain in the tragic tale of Alzheimer’s disease?

A long-neglected segment

For years, researchers have mainly paid attention to APP for the Aβ segment encoded in the amino acid sequence, like a dormant monster waiting to be unleashed. In the new research however, Angèle Parent, associate professor of neurobiology, and her team demonstrated that the other sections of a chopped-up APP strand matter too. One section plays a crucial role in consolidating spatiotemporal learning and memory in the brain, to the extent that it can prevent the onset of Alzheimer’s disease under the right circumstances.

This long-neglected segment, when tethered to the cell membrane, can participate in a signaling mechanism that triggers the formation of new memories. To promote this tethering, Parent and team fashioned a sticky lipid anchor protein from natural APP. This modified APP segment, called the mAICD, is simple in structure but has enormous functional consequences. Six months after newborn mice were injected with a virus that encouraged a high expression of mAICD in the brain, the results were surprising.

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