Researchers at the Gladstone Institutes have discovered how the APOE4 gene variant—carried by 25% of people and linked to up to 75% of Alzheimer’s cases—damages memory circuits long before symptoms appear.
The Discovery
- Protein Overproduction: APOE4 causes neurons to overproduce a protein called Nell2.
- Shrinkage & Hyperactivity: High Nell2 levels shrink neurons, making them overly sensitive and hyperactive. Young mice with high early hyperactivity went on to develop the worst memory loss.
- Neuron-Driven: The damage originates inside neurons themselves, not in supporting brain cells as previously thought.
Reversing the Damage
Using gene-silencing (CRISPRi) to lower Nell2 in adult mice restored neurons to their normal size and stabilized brain cell firing. This suggests early damage from APOE4 isn't permanent, offering a promising new target for early treatment before cognitive decline sets in.
Source: Science Daily
