The hippocampus plays a crucial role in the encoding, consolidation, and retrieval of episodic memories, which are the first to go missing in the early stages of Alzheimer’s disease. This study shows in transgenic mouse models of early Alzheimer’s disease that the amnesia is due to a defect in memory retrieval rather than in encoding. Importantly, the ‘forgotten’ memories can be rescued by direct activation of hippocampal dentate gyrus engram cells, and the amnesia correlates with a progressive reduction of dentate gyrus engram cell spine density. The authors suggest that selective rescue of dentate gyrus engram cells and their spine density may lead to new therapeutic strategies to recoup lost memories in early Alzheimer’s disease.
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