A major Alzheimer’s risk gene may shrink brain cells years before symptoms
Researchers have uncovered a possible reason why the Alzheimer’s risk gene APOE4 can disrupt the brain long before memory problems begin. In mice, APOE4 increased a protein called Nell2, shrinking neurons and making memory circuits unusually active. That early hyperactivity predicted worse memory later in life. Reducing Nell2 in adult mice reversed the abnormal changes, raising hopes for a new…
New research has discovered that the APOE4 gene variant, a major Alzheimer's risk gene, may shrink brain cells years before memory problems appear. Scientists at the Gladstone Institutes have mapped a molecular sequence showing how this gene variant could lead to early brain changes. In studies using mouse models, published in Nature Aging, APOE4 increased the production of a protein called Nell2, which caused neurons to become smaller and more active.
Mice with the greatest Nell2 levels when young later showed more severe memory issues. By reducing Nell2 levels, even in adult mice carrying APOE4, neurons returned to their normal size and firing behavior, suggesting that drugs targeting Nell2 may help people with APOE4 who face an elevated risk of Alzheimer's disease.
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