RESOLVING THE LEDGER
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0 Share Newsweek is a Trust Project member Scientists may have uncovered a crucial clue to one of the biggest mysteries in Alzheimer's disease: why some people develop dementia while others do not.
A new study published i n Nature Medicine analyzed donated brain tissue from older adults with and without cognitive decline, as well as cognitively healthy centenarians.
Their findings suggest that the way certain immune cells in the brain respond to Alzheimer's -related damage may play a key role in determining whether the disease progresses to dementia.
Dr. Steve Allder, a consultant neurologist who wasn't involved in the study, told Newsweek : "This is an encouraging piece of research that adds another important piece to the Alzheimer's puzzle."
Alzheimer's disease is often linked to the buildup of two proteins in the brain: amyloid plaques and tau tangles. But having these changes doesn't always mean someone will develop memory loss or dementia.
To investigate why some people remain mentally sharp despite Alzheimer's-related brain changes, researchers from Vlaams Instituut voor Biotechnologie, KU Leuven and Muna Therapeutics in Belgium, alongside the UK Dementia Research Institute, studied brain tissue from people with dementia, cognitively healthy older adults and centenarians.
They focused on microglia—the brain's immune cells—which help protect and monitor the brain. The researchers found that these cells behave differently as Alzheimer's develops.
They identified what appeared to be different stages of the disease. Early on, microglia switched into an inflammatory state linked to amyloid plaques—abnormal levels of this naturally occurring protein clump together to form plaques that disrupt cell function, according to the National Institute on Aging. Later, some microglia moved into a different immune state that appeared alongside tau buildup and brain cell damage.
The findings suggest this shift may be an important turning point that helps determine whether Alzheimer's-related changes in the brain eventually lead to dementia.
Allder, who works at Re:Cognition Health, in Birmingham, England, told Newsweek : "For many years, research has concentrated on removing amyloid plaques, but this work suggests that maintaining a healthy immune response within the brain could be just as important.
"If we can understand what allows these protective mechanisms to continue working, we may eventually be able to delay or even prevent symptoms, despite the presence of Alzheimer's pathology."
The researchers also found that people who remained mentally sharp despite having Alzheimer's pathology did not all follow the same pattern.
Some older adults who had amyloid plaques but no dementia showed the early microglial response but never moved into the later immune state linked to disease progression.
Meanwhile, cognitively healthy centenarians appeared to activate that later immune response, but it was largely not connected to tau buildup.
This suggests that resilience to Alzheimer's may not simply come from avoiding the disease-related changes in the brain. It may also depend on how the brain responds and adapts to those changes.
"Understanding better how the brain resists the disease will provide new avenues towards therapies to prevent neurodegeneration and dementia," said study corresponding author Professor Mark Fiers.
The findings could help guide future Alzheimer's treatments. Rather than focusing only on removing amyloid plaques, scientists may also look at ways to influence microglia and help preserve the immune responses associated with resilience.
"These findings open new opportunities to target microglial states—especially pathways such as TREM2—and extend resilience rather than simply focusing on plaque removal.
"We are excited to continue this journey and understand the causal role of microglial transitions leading to the identification of novel therapeutic approaches to delay or prevent disease progression," said Niels Plath, chief scientific officer of Muna Therapeutics, in a statement.
Vlaams Instituut voor Biotechnologie. (2026, July 26). A hidden Alzheimer’s tipping point may decide who gets dementia. ScienceDaily . Retrieved July 26, 2026 from www.sciencedaily.com/releases/2026/07/260726015257.htm Contact Newsweek editors on this story: Charlotte Nisbet and Emma Lee-Sang
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