New research from University College London (UCL) has revealed a significant link between memory impairment in Alzheimer’s disease and disruptions in how the brain replays recent experiences during rest. This groundbreaking study in mice shows that dysfunction in neurological processes essential for memory consolidation may underlie the cognitive deficits associated with the disease. The survey results are current biologycould pave the way for new drug treatments and diagnostic tools for early detection of Alzheimer’s disease.
Alzheimer’s disease is characterized by the buildup of harmful proteins and plaques in the brain, causing symptoms such as memory loss and difficulty in familiar environments. However, the specific mechanisms by which these plaques affect brain function remain largely unknown. Dr Sarah Shipley, co-lead author of the study, emphasized the importance of understanding how brain cell function changes in response to these pathological changes: “We wanted to understand how brain cell function changes as the disease progresses in order to identify what is causing these symptoms.”
The research focuses on the role of the hippocampus, a region important for learning and memory. During periods of rest, the brain typically replays recent experiences through specific neurons known as place cells. These place cells activate in patterns that reflect an individual’s experiences, making it easier to store those experiences as long-term memory. The research team sought to examine this regenerative activity in mice engineered to develop amyloid plaques, a hallmark of Alzheimer’s disease.
By monitoring the brain activity of mice navigating a simple maze, researchers were able to analyze how the regeneration process differs between healthy mice and mice with amyloid disease. Although regeneration events occurred with equal frequency in both groups, the organization of the regeneration signal in Alzheimer’s disease mice was found to be chaotic. Rather than memories becoming stronger, the activity between place cells became disorganized over time. This disruption was accompanied by a decrease in the reliability of individual neurons, especially after a resting period during which memories were consolidated through replay, disrupting their ability to consistently represent a particular location.
The behavioral effects of these neuronal changes were clear, with affected mice performing poorly in the maze. They often revisit previously explored paths, indicating an inability to accurately recall their journeys. Co-lead author Professor Caswell Barry said the findings revealed a breakdown in the way memories are consolidated in the brain. “We have uncovered a breakdown in the way the brain consolidates memories, visible at the level of individual neurons. It doesn’t mean the brain has stopped trying to consolidate memories; the process itself has gone wrong.”
The significance of this research goes beyond understanding the mechanism of memory loss in Alzheimer’s disease. The researchers are optimistic that their findings could lead to earlier detection methods and new treatments focused on restoring normal regenerative activity. The use of the neurotransmitter acetylcholine, which is targeted by existing Alzheimer’s disease drugs, may provide a path to more effective treatment. “We hope our findings will help develop tests to detect Alzheimer’s disease early, before large-scale damage occurs,” Barry said.
This enlightening research was carried out by scientists from UCL’s School of Life Sciences and School of Brain Sciences, with support from institutions including the Cambridge Trust, Wellcome and the Freemasons Charitable Foundation. As our understanding of Alzheimer’s disease advances, this study represents an important step toward addressing one of the disease’s most challenging aspects: its impact on memory.