A new study in mice suggests that memory problems in Alzheimer’s disease may stem from a breakdown in how the brain replays recent experiences during periods of rest. The research was carried out by scientists at University College London (UCL) and focuses on a brain process believed to be essential for forming and maintaining memories.
The findings, published today (January 29) in Current Biology, may help guide the development of new drug treatments aimed at this disrupted brain activity. They could also support efforts to create earlier diagnostic tests for Alzheimer’s, before major brain damage occurs.
How Brain Cells Change as Alzheimer’s Develops
Co-lead author Dr. Sarah Shipley (UCL Cell & Developmental Biology) explained that Alzheimer’s disease is driven by the accumulation of harmful proteins and plaques in the brain, which lead to symptoms such as memory loss and difficulty navigating familiar spaces. However, she noted that scientists still do not fully understand how these plaques interfere with normal brain function.
“We wanted to understand how the function of brain cells changes as the disease develops, to identify what’s driving these symptoms,” she said.
She also described the importance of a process that normally occurs when the brain is at rest. “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.”
The Role of the Hippocampus and Place Cells
This memory replay takes place in the hippocampus, a brain region critical for learning and navigation. It involves specialized neurons known as place cells, which activate in specific patterns to represent locations in an environment.
Place cells were discovered by Nobel prize-winning UCL neuroscientist Professor John O’Keefe. These neurons (brain cells) become active when an individual moves through a space, firing in a sequence that reflects the path taken. Later, during rest, the same cells typically reactivate in the same order, helping the brain store those experiences as lasting memories.
Tracking Memory Replay in a Maze Task
In the study, researchers evaluated how well mice could navigate a simple maze while recording brain activity at the same time. Using electrodes, they monitored around 100 individual place cells simultaneously as the animals explored and later rested.
This allowed the team to closely examine how memory-related brain activity differed between healthy mice and those with amyloid pathology linked to Alzheimer’s disease.
Disorganized Replay and Unstable Memory Signals
The results showed that memory replay was significantly altered in mice with amyloid plaques. Replay events still happened just as often as in healthy mice, but the activity patterns were no longer well organized. Instead of reinforcing memories, the signals were scrambled and poorly coordinated.
The researchers also found that place cells in affected mice became less reliable over time. Individual neurons stopped consistently representing the same locations, especially after rest periods, which are normally when memory replay strengthens these signals.
Memory Problems Linked to Brain Replay Failure
These changes had clear effects on behavior. Mice with disrupted replay performed worse on the maze task. They appeared to forget where they had already been and repeatedly explored paths that led nowhere.
Co-lead author Professor Caswell Barry (UCL Cell & Developmental Biology) said the findings reveal a breakdown in memory consolidation that can be seen at the level of individual brain cells.
“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.”
Toward Earlier Detection and Better Treatments
Professor Barry added that understanding this faulty replay process could lead to earlier detection of Alzheimer’s or new treatments aimed at restoring normal memory consolidation.
“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. We’re now investigating whether we can manipulate replay through the neurotransmitter acetylcholine, which is already targeted by drugs used to treat Alzheimer’s symptoms. By understanding the mechanism better, we hope to make such treatments more effective.”
Reference: “Disrupted hippocampal replay is associated with reduced offline map stabilization in an Alzheimer’s mouse model” by Sarah Shipley, Marco P. Abrate, Robin Hayman, Dennis Chan and Caswell Barry, 29 January 2026, Current Biology.
DOI: 10.1016/j.cub.2025.12.061
The study was carried out by researchers in the UCL Faculties of Life Sciences and Brain Sciences, with support from the Cambridge Trust, Wellcome, and the Masonic Charitable Foundation.
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