Study finds Alzheimer’s scrambles memory replay while the brain rests
When the brain is at rest, it does not become inactive. Instead, it normally replays recent experiences to help stabilize memory. A new animal study examines how this replay process changes in the context of Alzheimer’s disease. In simple terms, the study finds that Alzheimer’s disease disrupts how the brain replays recent experiences while it is at rest.
Note: This article is intended for general information and educational purposes. It summarizes scientific research in accessible language for a broad audience and is not an official scientific press release.
A new study published in Current Biology reports that memory problems in an Alzheimer’s disease mouse model are linked to changes in how the brain replays recent experiences during periods of rest. The research was conducted by Sarah Shipley, Marco P. Abrate, Robin Hayman, Dennis Chan, and Caswell Barry across multiple research units at University College London and the University of Cambridge, including the UCL Research Department of Cell and Developmental Biology, the UCL Institute of Neurology, the UCL Institute of Cognitive Neuroscience, and the MRC Cognition and Brain Sciences Unit at the University of Cambridge. By combining memory tasks with detailed recordings of individual brain cells, the researchers examined how patterns of brain activity during rest relate to memory performance.
The study focused on a knock-in mouse model that develops amyloid pathology characteristic of Alzheimer’s disease. According to the authors, these animals showed difficulties in spatial memory tasks, alongside reduced stability of hippocampal “place cells”- specialized brain cells that normally help keep track of locations. Importantly, the researchers found that while the brain continued to replay recent experiences during rest, these replay patterns were less organized than in healthy animals.
What the Researchers Investigated
The researchers aimed to better understand how memory-related brain activity changes as amyloid pathology develops, focusing on processes that support the stability of spatial memory over time. Rather than measuring memory outcomes alone, the study examined the underlying neural activity that helps maintain consistent representations of space.
A central focus was the hippocampus, a brain region essential for navigation and memory. In healthy conditions, groups of hippocampal neurons work together to form stable maps of the environment, and these maps are reinforced when the brain reactivates recent activity during periods of rest. The authors investigated whether this stabilizing process operates differently when amyloid pathology is present.
By analyzing both behavior and neural activity, the study explored how changes in the coordination and organization of hippocampal activity relate to performance on memory tasks. All experiments were conducted in mice, and the authors explicitly frame their findings as insights into neural mechanisms in an animal model, not as direct evidence about human memory or cognition.
How the Study Was Conducted
The study was carried out using AppNL-G-F knock-in mice, a model that develops amyloid pathology associated with Alzheimer’s disease without artificially increasing amyloid protein levels. Eight mice with this pathology and nine age-matched healthy mice took part in the experiments. All animals were trained to navigate a familiar eight-arm maze, a task commonly used to test spatial memory.
As the mice explored the maze and later rested, the researchers recorded brain activity using tiny implanted electrodes. These recordings captured signals from around one hundred individual nerve cells in a specific hippocampal region involved in memory and navigation. This approach allowed the researchers to observe both how the animals behaved and how single brain cells responded over time.
Memory performance was measured by tracking how often the mice returned to maze arms they had already visited. At the same time, the researchers analyzed how stable memory-related brain cells were and how groups of cells reactivated during rest. To do this, they applied established analytical methods to examine how well neurons were recruited, coordinated, and organized during replay events.
What Makes This Study New
Previous studies of Alzheimer’s disease models have mainly measured how often memory replay events occur, usually relying on indirect signals. This study instead examined what those replay events actually look like by recording the activity of individual brain cells.
According to the researchers, this is the first work to reconstruct replayed memory sequences at the cellular level in a modern amyloid knock-in mouse model and to link the organization of these replay patterns to the stability of spatial memory during rest. The results show that replay quality, not just replay frequency, is closely related to memory-related brain function.
Key Findings from the Study
According to the researchers:
- Memory performance was weaker in the Alzheimer’s model. Mice with amyloid pathology revisited maze arms they had already explored more often than healthy mice, showing poorer spatial memory during the task.
- Memory-related brain cells were less stable over time. Hippocampal “place cells” in these mice changed their activity patterns more from one moment to the next. This instability was especially clear after rest periods, when place cells in healthy mice normally became more stable.
- Memory replay still happened, but its organization was altered. Replay events during rest occurred just as often in both groups. However, in mice with amyloid pathology, fewer replay events formed clear, well-organized sequences, and these sequences captured less of the overall brain activity.
- Brain cells worked together less effectively during replay. Individual place cells were recruited into replay events less often, and pairs of neurons were less well coordinated. The researchers found that poorer replay organization and weaker cell coordination were linked to reduced stability of place cells across time.
Authors’ Conclusions
The researchers conclude that memory problems in this Alzheimer’s disease mouse model are linked to how well memory replay is organized during rest, not to how often replay happens. When brain cells do not work together in a coordinated way, memory-related representations become less stable.
They emphasize that the results show a relationship, not direct cause and effect. According to the authors, disrupted replay may be one of the processes connecting amyloid pathology to memory-related changes in the brain, but more research is needed to understand why replay becomes disorganized in the first place.
In comments reported by ScienceDaily, the authors explain that a better understanding of these brain mechanisms could, in the future, support research efforts aimed at earlier detection of Alzheimer’s disease or help guide studies focused on restoring normal memory replay activity during rest. They also note that ongoing work is examining whether this replay process can be influenced through neurotransmitter systems such as acetylcholine, a chemical messenger that plays a key role in how nerve cells communicate and that is already widely studied in Alzheimer’s research.
The information in this article is provided for informational purposes only and is not medical advice. For medical advice, please consult your doctor.
Reference:
Shipley S., Abrate M.P., Hayman R., Chan D., Barry C. Disrupted hippocampal replay is associated with reduced offline map stabilization in an Alzheimer’s mouse model. Current Biology, 2026. DOI: 10.1016/j.cub.2025.12.061
