Alzheimer's-linked protein can be cleared from mouse brains without ill effects

mouse

UT Southwestern researchers have removed a protein from the brains of mice with no harmful effects, suggesting that potential Alzheimer’s drugs targeting this protein could do so without affecting memory and learning.

The protein, apolipoprotein E, or APOE, is related to a higher risk of Alzheimer’s disease: A variant of APOE, known as APOE4, can drive the accumulation of toxic plaques in the brains of Alzheimer’s patients. And while other studies have focused on removing the protein to treat Alzheimer’s, it was unknown whether APOE is essential for healthy brain function.

APOE has multiple functions in the body, such as transporting cholesterol as well as the beta-amyloid that cluster together into plaques in the brains of Alzheimer’s patients. While the UT Southwestern team successfully cleared APOE from the brain without compromising memory or learning, removing it from other parts of the body raised cholesterol levels, which in turn blocked brain function, according to a statement. This confirms previous research that suggests cardiovascular health affects the brain.

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Although further research is needed to pinpoint just how cardiovascular issues, such as elevated cholesterol, cause changes in the brain, the findings, published in The Journal of Neuroscience, add weight to the theory that cutting APOE in the brain could lead to a viable therapy for Alzheimer’s disease.

"This approach still holds potential," said Dr. Joachim Herz, a professor of molecular genetics, neuroscience, neurology and neurotherapeutics at UT Southwestern’s O’Donnell Jr. Brain Institute, in the statement. Teams at UT Southwestern and other sites are currently seeking to unravel the effects that the removal of the APOE4 protein has on the brain and body.

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