Researchers at Gladstone Institutes say a common Alzheimer’s risk gene may start changing brain cells years before symptoms show up. Their findings, published in Nature Aging and reported by ScienceDaily, focus on APOE4, the strongest known genetic risk factor for Alzheimer’s disease.
In mouse studies, the team found that APOE4 led to higher levels of a protein called Nell2. That increase made neurons smaller and more active than normal, and mice with the highest early brain hyperactivity later had the worst memory problems.
The researchers also found that the changes could be partly reversed. When they lowered Nell2 production in adult APOE4 mice, the neurons grew larger and their activity moved back toward normal, according to the study.
The team says the effect was driven by APOE4 produced inside neurons, not astrocytes, which had long been suspected of playing the main role. The results suggest Nell2 could be a future target for therapies aimed at lowering Alzheimer’s risk in people who carry APOE4.
