Why can't Alzheimer's patients remember? Scientists may have found the answer

(CN) — When we rest after exploring a new place, our brains are hard at work. Neurons fire in rapid sequences, replaying our journey like a mental recording. Scientists believe this process is essential for turning experiences into lasting memories.

But in Alzheimer’s disease, this process falls apart, according to researchers from University College London. The findings, published Thursday in the journal Current Biology, suggest that the brain’s memory replay system doesn’t simply slow down or stop, it becomes fundamentally disorganized.

The discovery emerged from experiments with mice engineered to develop amyloid plaques, the harmful protein deposits that accumulate in the brains of Alzheimer’s patients. The mice do not develop Alzheimer’s itself but are widely used to model key features of the disease. Using arrays of electrodes to monitor about 100 individual neurons, researchers tracked the animals’ brain activity as they navigated a simple maze and then rested.

“When we rest, our brains normally replay recent experiences — this is thought to be key to how memories are formed and maintained,” said Sarah Shipley, co-lead author from UCL’s Cell & Developmental Biology department. “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.”

The replay process centers on specialized neurons called place cells, which fire when the animal is in a specific place. These cells create a neural map of the space. As a mouse explores, its place cells activate in sequence, marking its path. During rest periods, those same cells should reactivate in the same order, allowing the brain to practice the route.

What the researchers found in mice with Alzheimer’s-like amyloid pathology surprised them. The replay events occurred just as frequently as in healthy mice. But the structure of the events had deteriorated. The coordinated patterns that normally reinforce spatial memories were jumbled, as if the neural recording had been corrupted.

Individual place cells also became unreliable over time, no longer consistently representing the same locations, especially after rest periods. The affected mice struggled with the maze task, repeatedly wandering down dead-end corridors they had already explored.

“We’ve uncovered a breakdown in how the brain consolidates memories, visible at the level of individual neurons,” said co-lead author Caswell Barry, also from UCL’s Cell & Developmental Biology department. “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.”

The findings could lead to new approaches for detecting and treating Alzheimer’s disease. Because the disruption occurs at a fundamental level of brain function, it might be detectable before extensive damage occurs. This could enable earlier diagnosis when interventions are most effective.

The scientists are now exploring whether the replay process can be manipulated through acetylcholine, a neurotransmitter already targeted by existing Alzheimer’s medications. Current drugs that boost acetylcholine levels can provide some symptom relief for patients, but understanding the underlying mechanisms more precisely could lead to better treatments.

“We hope our findings could help develop tests to detect Alzheimer’s early, before extensive damage has occurred, or lead to new treatments targeting this replay process,” Barry said. “By understanding the mechanism better, we hope to make such treatments more effective.”

While the work was conducted in mice modeling key features of Alzheimer’s disease, the fundamental process of memory replay happens in humans as well, making the findings relevant to understanding how Alzheimer’s disrupts our memory.

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