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By Daniella Gray
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Some people have the telltale signs of Alzheimer's in their brains yet never develop dementia. Scientists think they may know why.
A new study published in Cell Stem Cell examined postmortem human brain tissue and identified a population of "immature" neurons that appear to be linked to cognitive resilience, potentially helping some people maintain normal thinking and memory despite accumulating Alzheimer's pathology.
Researchers focused on the hippocampus, a brain region critical for learning and memory that is heavily affected by Alzheimer's disease.
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They found that people who remained cognitively healthy despite having Alzheimer's-related brain changes had a greater abundance of these immature neurons, which displayed characteristics associated with younger, more adaptable brain cells.
The findings could help explain why an estimated 30 percent of people with Alzheimer's pathology never develop clinical symptoms.
"There is probably no single answer, but our data point to one candidate," Evgenia Salta, senior author of the study, told Newsweek. "In resilient brains, we find neurons that look more immature or ‘youthful’, and these cells may help keep the surrounding brain tissue healthy despite the presence of Alzheimer’s pathology."
Salta, from the Netherlands Institute for Neuroscience, said resilience is likely influenced by a combination of factors.
Genetics may strengthen cellular programs that help contain damage as it accumulates, while lifestyle factors such as physical exercise and lifelong learning may help build what scientists call "cognitive reserve," allowing the brain to better cope with disease.
"Both may also influence these immature neurons," Salta added.
The findings also add to growing evidence that Alzheimer's pathology does not inevitably lead to dementia.
While the disease is characterized by the buildup of abnormal proteins in the brain, researchers are increasingly interested in understanding why some brains are more resistant to their effects than others.
According to the study, the newly identified neurons showed distinct molecular signatures and appeared to track both Alzheimer's pathology and resilience, suggesting they could play an important protective role.
"The most interesting result is the comparison between people with Alzheimer’s dementia and people who had the same brain pathology but stayed cognitively intact," Dr. Daniel Fenton, Ph.D., who was not involved in the research, told Newsweek.
Fenton, who is the head of neuropsychological services at NewDays, said the resilient group showed more protective and anti-inflammatory cellular activity, while communication between these neurons and neighboring cells appeared to break down in those who developed dementia.
While any potential treatments remain years away, Salta believes the discovery could eventually reshape how scientists approach Alzheimer's therapies.
"The phenomenon of cognitive resilience itself changes how we think about Alzheimer’s, in that dementia may not be the unavoidable outcome of the pathology, but a trajectory that can potentially be modified," she said.
Fenton said the findings may also shift how scientists think about brain repair in later life. Rather than replacing lost neurons, these immature cells may help maintain a healthy environment in the hippocampus, supporting the idea of cognitive reserve.
If the cells are ultimately confirmed to have a protective role, future therapies could focus not only on reducing damage caused by Alzheimer's but also on boosting the brain's own repair mechanisms.
"If these cells prove protective, therapies could shift from only limiting damage that has already occurred to also supporting the brain’s own repair mechanisms, its own arsenal," Salta said. "How much that helps would depend on how early we intervene, from delaying the onset of symptoms to reducing their severity."
Reference
Tosoni, G., Ayyildiz, D., Snoeck, S., Moreno-Jiménez, E.P., Penning, A., Santiago-Mujika, E., Ruiz Ormaechea, O., Lee, H., Poovathingal, S., Davie, K., Bryois, J., Macnair, W., Anink, J., De Vries, L.E., Farmand, S., Nutma, E., Swaab, D.F., Aronica, E., Middeldorp, J., Thuret, S., Roybon, L., Basak, O., Fitzsimons, C.P., Lucassen, P.J. and Salta, E. (2026). Transcriptional profiles of immature neurons in aged human hippocampus track Alzheimer’s pathology and cognitive resilience. Cell Stem Cell, [online] 33(5), pp. 763–783.e9. doi:10.1016/j.stem.2026.04.002.
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