The loss of episodic memories in the early stages of Alzheimer’s disease (AD) results from impaired retrieval, rather than encoding, of information, reports a paper published online this week in Nature. The study, conducted in mouse models of early AD, demonstrates that forgotten memories can be rescued by directly activating specific cells in the hippocampus.
Several studies have suggested that the inability to remember an event (episodic memory) observed in AD patients is a result of ineffective encoding of new information. However, because cognitive tests rely on memory retrieval, it has been unclear whether it is poor encoding or poor retrieval of information that contributes to memory impairments.
Susumu Tonegawa and colleagues address this question by studying three different types of transgenic mice, which are amnesic and fail long-term memory tests. They find that optogenetically stimulating hippocampal dentate gyrus engram cells leads to the restoration of memory in early AD mice, such that they perform as well as control mice in a contextual fear-conditioning task. The authors report that spine density of dentate gyrus engram cells is correlated with amnesia in early AD and that without these cells, the rescue of long-term memory is not possible. They note that further research is needed to determine whether the long-term maintenance of memory storage declines as the disease progresses and to examine the mechanisms underlying cognitive impairments in non-episodic memory.