Alzheimer’s-Related Memory Concerns Linked to Glitches in the Brain’s Replay Process
Problems in the brain’s “rereading” process may cause the memory problems and navigation difficulties often associated with Alzheimer’s disease.
This is the conclusion of researchers studying the impact of the formation of amyloid plaques on memory in mouse models. The results were published in the journal Current biology.
“We discovered a dysfunction in the way the brain consolidates memories, visible at the level of individual neurons,” Caswell Barry of University College London Cell & Developmental Biology, UK, said in a statement.
“What is striking is that repetition events still occur, but they have lost their normal structure. It’s not that the brain stops trying to consolidate memories; the process itself has gone wrong.”
The findings could have major implications for developing new drugs to manage memory-related symptoms and creating tests to diagnose the disease in its early stages.
Learn more: Non-invasive sound therapy helps target Alzheimer’s plaques in monkeys — Could it one day help humans?
How the brain creates memories
The reason you can remember your trip around town without a map is thanks to a group of neurons stored in the brain’s hippocampus called place cells.
Place cells are tied to specific locations and play a key role in navigation. When you visit a new city, for example, certain location cells will light up and activate in a sequence. Then, later, when you rest, these same cells will light up in the same order. Essentially, your brain consolidates and strengthens your memory by replaying the experience. If you recall the memory later, the same cells will reactivate in the same order.
Alzheimer’s disease, however, appears to disrupt the proofreading process, which could explain why memory loss and navigation difficulties are among the first signs of the disease.
“We wanted to understand how brain cell function changes as the disease develops, to identify what is causing these symptoms,” Sarah Shipley of University College London Cell & Developmental Biology, UK, said in a statement.
“We found that this repetition process is disrupted in mice engineered to develop the amyloid plaques characteristic of Alzheimer’s disease, and this disruption is associated with the animals’ poor performance on memory tasks.”
Testing memory performance in mice
The team tracked the mice’s performance during a maze task. The goal was to find rewards placed in four of the eight arms extending from the center of the maze. The researchers were able to measure the activity of around 100 cells using electrodes.
People with an amyloid pathology that mimics the effects of Alzheimer’s disease have had the proofreading process disrupted. The sequence was garbled. Meanwhile, the place cells themselves were less stable and did not necessarily correspond to the same locations over time. In practice, this meant that the mice performed significantly worse in the maze task: individuals seemed to forget where they were and tried multiple times to reach dead ends.
Interestingly, the researchers note that the repetition events occurred equally often in both groups of mice. The difference was that the replay process consolidated memories in healthy mice. Whereas in sick mice, this is not the case. The contrast was particularly striking after rest periods.
Future research on Alzheimer’s disease
Although it should be noted that the research took place in animal models, the team hopes that these results could one day lead to the discovery of new drugs and treatment options targeting the brain’s proofreading process.
The results could also contribute to the development of tests to detect Alzheimer’s disease earlier, which would be particularly beneficial given the development of anti-amyloid immunotherapies. These promise to delay the progression of the disease and modify its course, but only if they are detected early enough.
“We are currently investigating whether we can manipulate replay via the neurotransmitter acetylcholine, which is already targeted by drugs used to treat symptoms of Alzheimer’s disease,” Barry said.
“By better understanding the mechanism, we hope to make these treatments more effective.”
This article does not offer medical advice and should be used for informational purposes only.
Learn more: Blood-brain barrier repair reversed Alzheimer’s disease in mice, a promising result for humans
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