If people over 80 with exceptional memory—a group who Northwestern researchers call “super-agers”—had a symbol in the style of Superman’s “S”, it might be the “super neurons” in their brains. The brains of super-agers age more slowly than normal, though until now no one understood what cellular trait qualified someone to be in this unique group. A new study published September 30 in The Journal of Neuroscience found that super-agers have significantly larger neurons in a specific brain region compared to the neurons of people of the same age and of individuals 20 to 30 years younger. 

The brain area in question, the entorhinal cortex, acts as a hub for consolidating new memories into long-term ones. It’s also one of the first targets of Alzheimer’s disease. Senior author Tamar Gefen, an assistant professor of psychiatry and behavioral sciences at the Northwestern University Feinberg School of Medicine, says her team was interested in looking at the entorhinal cortex in super-agers because their exceptional brain may hold a clue on what makes a person resistant to Alzheimer’s disease. 

The study examined six brains of recently deceased super-agers, seven cognitively average older adults of similar age, six young individuals, and five individuals with early Alzheimer’s. The researchers’ focused on the six layers of the entorhinal cortex, each with its own role in memory. In layer II of the entorhinal cortex, the researchers observed larger and healthier neurons than you would normally see in this brain area. 

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“What surprised me most was that neurons in the entorhinal cortex of super-agers were significantly larger than neurons found in individuals much younger—as young as age 27,” Gefen explains. While not directly tested in the study, the research authors suggest these super neurons may be a unique biological signature that’s imprinted on a super-ager since birth.

Unlike other cells, these large layer II neurons remained healthy and large throughout life and were significantly more resistant to the formation of tau tangles, large clumps of protein that accumulate inside neurons. Super-agers showed fewer tau tangles in layer II of the entorhinal cortex compared to people of similar ages. According to the researchers, the difference in tau tangle density could explain why some cells shrink and others stay large and healthy.

In healthy cells, tau proteins bind and stabilize microtubules, cylindrical structures that give cells their shape and help transport nutrients. But in early-stage Alzheimer’s, tau proteins detach from microtubules and stick to other tau molecules, eventually forming tangles that block the transport system and cause the cell to die. These deaths can weaken communication between neurons.

[Related: What the recording of a dying human brain could tell us]

“The presence of these structurally distinct nerve cells in ‘super-agers’ that do not show age-related cognitive decline, and very often evidence superior cognitive (memory) capability, may be significant,” notes James Giordano, a professor of neurology and biochemistry at Georgetown University Medical Center who was not affiliated with the study.

The next question to answer will be why some people grow these super-sized cells while others do not. This will involve probing the cellular environment and finding out the mechanism behind these neurons’ resiliency.

Understanding how super-agers stay sharp may help scientists one day create treatments to ensure a person’s brain stays cognitively resilient. Future research will also have to expand to other brain areas involved in memory to paint a more complete picture of how super-agers ward off neurodegenerative diseases. By doing so, Giordano says, this could open up a new realm of interventions that could potentially preserve cognitive function across the lifespan while identifying individuals at most risk of age-related cognitive decline.

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