It is known that one of the earliest sites of Alzheimer’s disease pathology is the hippocampus, a brain structure critical for the learning and memory processes that falter early in Alzheimer’s disease. The apoE4 gene creates a protein of the same name that markedly increases a person’s risk for Alzheimer’s disease and occurs in 65%-80% of people with Alzheimer’s disease. ApoE4 protein is the major genetic risk factor for Alzheimer’s disease, however, the mechanism by which it causes cognitive decline and disrupts hippocampal memory processes is unclear. Now, a study from researchers at the Gladstone Institutes shows that the apoE4 protein changes the activity of neurons in the hippocampus. The team state that in this region, apoE4 decreases two types of brain activity that are important for memory formation, namely, sharp wave ripples and coincident slow gamma activity. The opensource study is published in the journal Neuron.
The current study 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. Results show that the mice exhibited normal slow gamma activity despite having fewer ripples. Data findings show that 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.
The team surmise that their findings suggest disrupted slow gamma activity during ripples is a major consequence of apoE4 expression that likely impairs memory consolidation. For the future, the researchers state that with this knowledge, the global medical community can now work toward correcting or restoring slow gamma activity in the hippocampus to prevent or alleviate memory loss in Alzheimer’s disease.
Source: Gladstone Institutes