Mice with apoE4 had fewer ripples than mice with the normal apoE3 protein, and they had less slow gamma activity during the ripples. Based on these results, the scientists questioned whether these differences in activity affected the ability to form and replay memories. Image is for illustrative purposes only. Image is credited to Andrews-Zwiling Y. et al./Journal of Neuroscience, and is adapted from the Gladstone Institute video.
Scientists at the Gladstone Institutes have discovered how the major genetic risk factor for Alzheimer’s disease causes memory impairment. A specific type of brain activity important for memory replay is disrupted in mice with the E4 version of the apolipoprotein E (apoE4) gene, which may interfere with memory formation. The apoE4 gene creates a protein of the same name that markedly increases a person’s risk for Alzheimer’s and occurs in 65%-80% of Alzheimer’s disease.
In the new research they found apoE4 protein changes the activity of neurons in the hippocampus. It decreases 2 types of brain activity that are important for memory formation: sharp wave ripples (ripples) and coincident slow gamma activity. During the ripples, prior experiences are replayed numerous times to help preserve the memory of them, and the slow gamma activity that occurs during the ripples helps to ensure that the replay of those memories is accurate.
“When we experience something new, cells in the hippocampus fire in a particular order. Later, these same cells fire over and over again in the same order to replay the event, which helps consolidate the memory so we don’t forget it,” explained Anna Gillespie, PhD. “Slow gamma activity that occurs during the ripples organizes the firing of these cells. If this activity is disrupted, the playback will be disorganized, compromising the memory.”
Mice with apoE4 had fewer ripples than mice with the normal apoE3 protein, and they had less slow gamma activity during the ripples. Based on these results, the scientists questioned whether these differences in activity affected the ability to form and replay memories.
Method: They tested mice that expressed apoE4 in all cells except inhibitory neurons in the hippocampus. From earlier research, the scientists knew that these mice showed no signs of inhibitory neuron death in the hippocampus, and their ability to learn and form memories was not impaired. In the current study, the mice showed normal slow gamma activity despite having fewer ripples. Thus, slow gamma activity—the coordination of cell firing during playback—appears to be a critical factor in memory consolidation, rather than the number of replay events from the ripples.
“Our research suggests that disrupted slow gamma activity during ripples is a major consequence of apoE4 expression that likely impairs memory consolidation,” said senior author Yadong Huang, MD, PhD, a senior investigator at Gladstone. “With this knowledge, we can now work toward correcting or restoring slow gamma activity in the hippocampus to prevent or alleviate memory loss in Alzheimer’s disease.” http://neurosciencenews.com/apoe4-memory-genetics-alzheimers-4182/
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