Memory problems in Alzheimer’s may be linked to disrupted brain replay during rest, new research suggests.
The study, conducted in mice, points to a disrupted brain process that normally helps strengthen and preserve memories.
Researchers say the findings could inform future drugs that target this malfunctioning process and guide tools for earlier detection.
Scientists at University College London (UCL) found that replay events occurred as often in mice with amyloid plaques (protein deposits linked to Alzheimer’s) as in healthy mice, but the underlying patterns were no longer organised.
Instead of reinforcing memories, the coordinated activity of place cells became scrambled.
Dr Sarah Shipley, co-lead author from UCL Cell and Developmental Biology, said: “Alzheimer’s disease is caused by the build-up of harmful proteins and plaques in the brain, leading to symptoms such as memory loss and impaired navigation, but it’s not well understood exactly how these plaques disrupt normal brain processes.
“We wanted to understand how the function of brain cells changes as the disease develops, to identify what’s driving these symptoms.
“When we rest, our brains normally replay recent experiences, this is thought to be key to how memories are formed and maintained.
“We found this replay process is disrupted in mice engineered to develop the amyloid plaques characteristic of Alzheimer’s, and this disruption is associated with how badly animals perform on memory tasks.”
This replay activity takes place in the hippocampus, a region essential for learning and memory. During rest, specific neurons known as place cells activate in rapid sequences that mirror recent experiences.
Place cells, discovered by Nobel Prize-winning UCL neuroscientist Professor John O’Keefe, are neurons that correspond to particular locations.
As a person or animal moves through a space, different place cells fire in sequence. Later, during rest, those same cells typically reactivate in the same order, helping the brain store the experience as a memory.
To study this process, researchers tested how mice performed in a simple maze while recording brain activity at the same time.
Using specialised electrodes, they monitored roughly 100 individual place cells simultaneously as the animals explored and then rested.
This approach allowed the team to compare normal replay patterns with those seen in mice that had developed amyloid pathology associated with Alzheimer’s disease.
The researchers also observed that place cells in affected mice grew less stable over time. Individual neurons stopped reliably representing the same locations, especially after rest periods, which are normally when replay should strengthen memory signals.
These changes had clear behavioural effects.
Mice with disrupted replay performed worse in the maze, frequently revisiting paths they had already explored and appearing unable to remember where they had been.
Professor Caswell Barry, co-lead author from UCL Cell and Developmental Biology, said: “We’ve uncovered a breakdown in how the brain consolidates memories, visible at the level of individual neurons.
“What’s striking is that replay events still occur, but they’ve lost their normal structure. It’s not that the brain stops trying to consolidate memories, the process itself has gone wrong.”
Professor Barry added that the findings may help researchers identify Alzheimer’s earlier or develop treatments that focus on restoring normal replay activity.
