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…
A study published in Nature Aging has revealed that the APOE4 gene variant may begin altering brain cells years before Alzheimer's symptoms appear. Researchers at Gladstone Institutes found that APOE4 increases the production of a protein called Nell2, causing neurons to become smaller and hyperactive. Mice with higher Nell2 levels when young later developed more severe memory problems.
When researchers reduced Nell2 production in adult mice with APOE4, their neurons returned to normal size and firing behavior. This suggests APOE4 accelerates a process resembling normal aging, potentially explaining why people with the gene variant develop Alzheimer's earlier. The study also found that APOE4 is produced within neurons themselves, not by astrocytes, challenging previous beliefs.
Researchers say that lowering Nell2 levels in adult mice with APOE4 reversed the detrimental effects, hinting at a potential window for early intervention.
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