AI Insight
Researchers found that the Alzheimer's risk gene APOE4 causes neurons to shrink and memory circuits to become hyperactive years before symptoms appear by increasing levels of a protein called Nell2. In mouse studies, this early hyperactivity in brain circuits predicted poorer memory performance later in life. Importantly, reducing Nell2 levels in adult mice successfully reversed these abnormal brain changes.
Why it matters
This discovery identifies a potential therapeutic target for intervening in Alzheimer's disease before cognitive symptoms develop in people carrying the APOE4 gene variant. The reversibility of these changes in adult mice suggests a window of opportunity for preventive treatments that could modify disease progression.
Understand the Science
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 way to intervene before Alzheimer’s progresses.
Source: A major Alzheimer’s risk gene may shrink brain cells years before symptoms