New research indicates that carrying the APOE4 gene variant, a significant risk factor for Alzheimer's disease, can alter neuron activity and brain function years before cognitive symptoms emerge. In young mice genetically engineered to carry APOE4, scientists observed that specific neurons in the hippocampus, a key memory center, were smaller and hyperactive. This disruption is linked to a protein called Nell2. Researchers found that blocking Nell2 production in these mice reversed the neuronal damage and restored normal brain activity. This discovery suggests a potential pathway for early intervention and treatment of Alzheimer's, as the damage may not be irreversible. The findings offer a deeper understanding of how APOE4 impacts neuronal function at an early age, potentially paving the way for therapies to counteract its detrimental effects.
Neuroscientist Dennis Tabuena at work.
The study, published in Nature Aging, compared APOE4 mice to those with the less risky APOE3 variant. While APOE3 neurons also showed increased activity with age, they did not develop the cognitive problems seen in APOE4 mice. The abundance of Nell2 in APOE4 neurons is believed to be the molecular mechanism driving premature brain aging. The ability to reverse these disease manifestations by lowering Nell2 levels in adult mice provides a promising outlook for future Alzheimer's treatments.