Stanford Scientists Discover How Alzheimer's Tricks Brain Into Erasing Memories

Researchers at Stanford University have uncovered a critical molecular mechanism that explains how Alzheimer's disease destroys memories, revealing that both amyloid beta and brain inflammation converge on a single receptor that signals neurons to prune their own connections. The groundbreaking discovery, published in the Proceedings of the National Academy of Sciences, offers a promising new target for treatment.

The study led by Carla Shatz, Sapp Family Provostial Professor at the Wu Tsai Neurosciences Institute, identified the LilrB2 receptor as the common pathway through which both amyloid beta plaques and inflammatory molecules trigger memory loss. Research scientist Barbara Brott discovered that the complement cascade protein C4d, previously thought to have no function, binds to this receptor with high affinity and actively strips synapses from neurons.

In experiments where C4d was injected into healthy mouse brains, the protein caused dramatic synapse loss, demonstrating that neurons are not passive victims in Alzheimer's progression. Shatz emphasized this finding, stating that neurons are active participants in their own destruction rather than innocent bystanders being attacked by external forces.

The discovery challenges current treatment approaches that focus primarily on breaking up amyloid plaques. Shatz noted that existing FDA-approved Alzheimer's drugs targeting plaques have shown limited effectiveness and carry significant side effects including headaches and brain bleeding. The new research suggests that directly targeting receptors like LilrB2 to protect synapses could prove far more effective.

This breakthrough has significant implications for the more than 55 million people worldwide living with dementia, the majority of whom have Alzheimer's disease. By identifying the molecular switch that triggers synapse pruning, researchers have opened a new avenue for developing therapies that could preserve memory by blocking this destructive pathway before connections between brain cells are permanently lost.