Why some brains resist dementia despite Alzheimer’s: study points to ‘immature’ neurons’ response

Some people remain mentally sharp even as Alzheimer’s disease builds up in their brains. New research from the Netherlands Institute for Neuroscience suggests that this resilience may depend less on producing more new brain cells and more on how a rare set of “immature” neurons respond to damage.

The work, published in Cell Stem Cell, probes a long-standing puzzle in neuroscience: why some older adults with Alzheimer’s pathology never develop dementia. “Around 30% of older adults who develop Alzheimer’s disease never experience its symptoms,” said last author Evgenia Salta.

“We really don’t know why. That’s a big mystery, and a very important one.” Salta’s team examined human brain tissue from the Netherlands Brain Bank, including samples from control donors without brain pathology, patients diagnosed with Alzheimer’s, and individuals who had Alzheimer’s pathology but remained resilient to developing dementia.

The researchers focused on a small part of the brain’s memory center that is thought to be one of the few regions where new neurons can form in adulthood—a process known as adult neurogenesis, whose existence in humans has been debated. Because these cells are extremely rare, the team developed new ways to spot them and used analysis methods designed to identify them without relying too heavily on assumptions drawn from animal research.

They found immature neurons—cells that resemble young, not fully developed neurons—in all groups, even at an average donor age of over 80. The surprise was not their presence, but their behavior. The researchers expected to see many more immature neurons in resilient individuals than in Alzheimer’s patients, but the difference was smaller than anticipated.

Instead, the key distinction appeared to be functional: in resilient individuals, the cells activated programs associated with survival and coping with damage, and showed lower signals related to inflammation and cell death, according to Salta. That pattern points to a more nuanced picture of resilience.

“It might not be (only) about replacing lost neurons,” Salta said. The immature neurons may help sustain the surrounding tissue and keep the brain functional and “youthful,” acting “as a sort of fertilizer in a garden that has started falling apart.” Salta cautioned that the study cannot directly test what these cells do.

“We assume the cells’ function based on the data, but we cannot confirm it in this type of study,” she said, emphasizing that the findings represent “one piece of a very large puzzle.” The team notes that resilience is unlikely to hinge on a single factor, but the results outline cellular programs that could help guide future research into how the aging brain copes with disease.