The study, published in Nature Aging by researchers at Gladstone Institutes, reveals that the APOE4 gene variant—known as the strongest genetic risk factor for Alzheimer’s disease—may begin altering brain activity long before cognitive symptoms manifest. Utilizing mouse models, the researchers identified that APOE4 increases production of the protein Nell2, leading to neuronal shrinkage and heightened activity. Mice exhibiting the most significant brain hyperactivity in youth subsequently developed the most severe memory impairments, suggesting a causal link between early neural changes and later cognitive decline.

Further investigation demonstrated that reducing Nell2 production could mitigate these effects. Even in adult mice carrying APOE4, diminishing Nell2 levels restored neurons to a more normal size and activity pattern. This finding implies that therapeutic strategies targeting Nell2 might ameliorate the elevated Alzheimer’s risk associated with APOE4. The researchers also clarified that the hyperactivity and neuronal changes are driven by APOE4 produced within neurons themselves, rather than by astrocytes, challenging previous assumptions about the gene’s mechanism of action. Source

This is a summary. Read the original at sciencedaily.com.