Silent Engrams and Alzheimer's: Unlocking Hidden Memories

    When we think of Alzheimer's disease, we often imagine erased memories and forgotten faces. But Dr. Stephanie Grella proposed challenging that view. This semester we had the opportunity to listen to her talk, where Dr. Grella explored a captivating idea: that memories in Alzheimer's may not disappear at all. Instead, they might remain preserved in the brain, simply inaccessible, locked behind what scientists call silent engrams. 

    An engram is the physical trace of a memory, a network of neurons that undergo chemical and structural changes during an experience. These neural clusters act as the brain's storage files, encoding events, emotions and knowledge. Normally, when we recall something, these neurons are reactivated, bringing the stored experience back into awareness. But what happens when that recall mechanism fails? According to Dr. Grella's study, in conditions like Alzheimer's, the engram (memory itself) might still exist, but the natural pathway to access it is disrupted. 

    A study I found that addresses this idea of engrams is the recent article published in Progress in Neurobiology (2024), "Memory Circuits in Dementia: The Engram, Hippocampal Neurogenesis and Alzheimer's Disease" by Lazarov et al. This study examines how Alzheimer's affects the hippocampus, the brain's memory center and focuses on how engram cells behave in both healthy and diseased brains. Surprisingly, these researchers found that even in Alzheimer's models, these engram cells often remain intact. Using techniques such as optogenetics and in vivo calcium imaging, the researchers were able to artificially reactivate dormant memory cells and restore previously "lost" memories in animal models. Their findings suggest that Alzheimer's does not always destroy memories but simply makes them inaccessible through normal biological cues. 

    Together, Dr. Grella's insights and Lazarov et al. contribute to a more nuanced understanding of Alzheimer's, replacing irretrievable loss with the possibility of recovery. If memories are truly locked away in silent engrams, future therapies could aim to reactivate what remains, instead of reconstructing what is believed to be lost. Techniques that restore neural connectivity, stimulate hippocampal neurogenesis or precisely target dormant engram cells could one day help patients recover memories thought to be lost forever. 

    In this new view of Alzheimer's, the past is not erased; it simply remains silent. As neuroscience contributes to unlock the mechanisms of memory, we may find that the stories, faces and moments we thought were gone are still there, waiting patiently for the brain and science to remember how to find them.

References

Josselyn, S. A., & Tonegawa, S. (2020). Memory Engrams: Recalling the Past and Imagining the Future. Science, 367(6473). https://doi.org/10.1126/science.aaw4325

Lazarov, Orly, et al. “Memory Circuits in Dementia: The Engram, Hippocampal Neurogenesis and Alzheimer’s Disease.” Prog Neurobiol, 3 July 2024, pmc.ncbi.nlm.nih.gov/articles/PMC11221328/.