A major Alzheimer’s risk gene may shrink brain cells years before symptoms
Researchers have identified that the APOE4 gene, a major Alzheimer's risk factor, causes neurons to shrink and become hyperactive long before memory symptoms appear. The study suggests that targeting the protein Nell2 could potentially reverse these early cellular changes.
Why it matters
This discovery provides a potential therapeutic target for early intervention in individuals genetically predisposed to Alzheimer's disease.
Millions of people carry APOE4, the strongest known genetic risk factor for Alzheimer's disease. New research suggests the gene variant may begin altering brain activity well before memory problems become noticeable.
Researchers at Gladstone Institutes have now mapped out a molecular sequence that could help explain these early effects. Their findings also point to a possible way to reverse some of the changes.
In a study using mouse models, published in Nature Aging, the researchers found that APOE4 increases production of a protein called Nell2. Higher Nell2 levels caused neurons to become smaller and unusually active. Mice with the greatest brain hyperactivity when they were young later developed the most severe memory problems.
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