Glitches in the brain’s “replay” process may be behind the memory impairments and navigational difficulties often associated with Alzheimer’s disease.
This is the conclusion of researchers studying the impact of amyloid plaque formation on memory in mouse models. The results have been published in the journal Current Biology.
“We've uncovered a breakdown in how the brain consolidates memories, visible at the level of individual neurons,” said Caswell Barry from University College London Cell & Developmental Biology, U.K., in a statement.
“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."
The findings could have major implications for developing new drugs to manage memory-related symptoms and for creating tests that can diagnose the disease in its early stages.
How the Brain Makes Memories
The reason you can recall your journey into town without a map is thanks to a group of neurons stored in the brain’s hippocampus, known as 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 place cells will light up and activate in a sequence. Then, later, when you are resting, those same cells will light up in that same sequence. Essentially, this is your brain consolidating and strengthening your memory by replaying the experience. If you recall the memory at a later point, the same cells will reactivate in the same sequence.
Alzheimer’s, however, appears to disrupt the replay process — a fact that may explain why memory lapses and navigation difficulties are among the early signs of the disease.
“We wanted to understand how the function of brain cells changes as the disease develops, to identify what's driving these symptoms,” said Sarah Shipley from University College London Cell & Developmental Biology, U.K., in a statement.
“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."
Testing Memory Performance in Mice
The team tracked the performance of mice during a maze task. The goal was to find rewards placed in four of the eight arms extending from the maze’s centre. The researchers were able to measure the activity of approximately 100 place cells using electrodes.
Those with an amyloid pathology that mimics the effects of Alzheimer’s saw the replay process disrupted. The sequence was scrambled. Meanwhile, the place cells themselves were less stable and did not necessarily correlate to the same locations over time. In practice, this meant the mice performed significantly worse on the maze task – individuals appeared to forget where they had been and attempted dead ends multiple times.
Interestingly, the researchers note that replay events occurred just as often in both groups of mice. The difference was that the replay process consolidated memories in the healthy mice. Whereas in the diseased mice, it did not. The contrast was particularly stark after rest periods.
Future Alzheimer’s Research
While it should be noted that the research took place in animal models, the team hopes these findings could one day lead to the discovery of new drugs and treatment options targeting the brain’s replay process.
The results could also contribute to the development of tests that detect Alzheimer’s earlier, which would be particularly beneficial given the development of anti-amyloid immunotherapies. These promise to delay disease progression and modify disease outcome, but only when caught early enough.
“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,” said Barry.
“By understanding the mechanism better, we hope to make such treatments more effective."
This article is not offering medical advice and should be used for informational purposes only.
Read More: Repairing the Blood Brain Barrier Reversed Alzheimer's Disease in Mice, a Hopeful Result for Humans
Article Sources
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- This article references information from a recent study published in Current Biology: Disrupted hippocampal replay is associated with reduced offline map stabilization in an Alzheimer’s mouse model
