Memory replay disruption in the brain may be a key factor behind memory problems seen in Alzheimer's disease, according to new research from University College London (UCL). The study, published in Current Biology, investigated how the brain processes recent experiences during rest and found that this mechanism is impaired in mice with Alzheimer's-like pathology.
Dr. Sarah Shipley of UCL Cell & Developmental Biology, co-lead author of the study, explained: "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."
The researchers focused on place cells within the hippocampus. These neurons are responsible for representing specific locations and fire in sequences both when an animal moves through an environment and later during periods of rest. This sequence replay is believed to help consolidate memories.
To assess changes related to Alzheimer's pathology, scientists monitored about 100 individual place cells while mice navigated a simple maze. In mice with amyloid plaque build-up—a hallmark of Alzheimer’s—the frequency of replay events was similar to healthy controls. However, these events were less organized; patterns needed for reinforcing memories were scrambled rather than coordinated.
Additionally, affected mice showed less stability among their place cells over time. Neurons no longer reliably represented the same locations after rest periods—precisely when replay should strengthen those representations. As a result, these mice performed worse on maze tasks by forgetting previous paths taken and revisiting dead ends.
The study was conducted by teams from UCL Faculties of Life Sciences and Brain Sciences with support from organizations including the Cambridge Trust, Wellcome Trust, and Masonic Charitable Foundation.
