Engrams and Alzheimer's Disease Correlation

 

During the third week of our Neuroscience Seminar class, we had the honor of discussing what I believe to be the most interesting topic we have covered thus far: memory recall and storage through engrams. Dr. Stephanie Grella thoroughly presented this fascinating phenomenon of engrams to our class. We learned that her experiment essentially allowed her and her colleagues to determine whether or not the reactivation of the selected neurons was enough to recall previous memories. During the discussion, she described the process of using the fear conditioning tactic and different contexts to test her hypothesis (which we learned from the research article “​​Memory engrams: Recalling the past and imagining the future” and Grella's presentation that her hypothesis was accurate).  

​    In the article, “He Was Expected to Get Alzheimer’s 25 Years Ago. Why Hasn’t He?”, Pam Belluck discusses the interesting story of Doug Whitney, an individual with a rare genetic mutation that ensured he would develop Alzheimer's disease, and remained healthy for 25 years longer than his doctors had anticipated, given his condition and family history. Researchers ran numerous tests on him and believed that because of his high level of heat shock proteins, strong immune system, and the insinuation of amyloid and tau decoupling, he was able to stay healthy for a longer period. This, of course, opened up a variety of doors to discovering prevention and treatments for individuals at risk of early-onset Alzheimer's disease. The article also mentioned that Whitney’s son inherited the genetic mutation, but even at the age of 53, he remains relatively healthy and appears to show no signs of Alzheimer's disease. They found similar traits from his fathers tests in him, which would further explain why he remains unaffected by the mutated gene.

​    The study involving Doug Whitney relates to Dr. Stephanie Grella’s engram study in a number of interesting ways. One of Grella's main focuses was the discovery of silent engrams, a term used to describe the ability for memories to exist, but not be accessible. This is typically caused by disrupting synaptic strengthening. From this came the attempt to artificially reactivate these silent engrams by using fear conditioning in hopes of allowing the mice in the experiment to retrieve past memories. This relates to Whitney's case because, as I have previously mentioned, one of the factors as to why researchers believed he has managed to stay healthy for so long is that he has a significantly low tau protein accumulation, which in turn indicates amyloid and tau decoupling in his body. This would then imply that this process of disrupting the synaptic strengthening is being prevented, allowing his memories to be completely accessible, even with an amyloid burden. Along with this, it was found that many of the concepts that are protecting Whitney from getting Alzheimer's are also essential factors for engram formation.

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

(Belluck and Brauer)

Belluck, Pam, and M Scott Brauer. “He Was Expected to Get Alzheimer’s 25 Years Ago. Why Hasn’t He?” The New York Times, 7 Oct. 2025, www.nytimes.com/2025/10/07/health/alzheimers-gene-mutation.html.