A puzzling discovery has left doctors scratching their heads: The brain of an American woman with Down syndrome showed all the classic signs of Alzheimer’s disease, yet she remained symptom-free throughout her lifetime.
The patient enrolled in the Alzheimer Biomarker Consortium–Down Syndrome, which was created to explore how the two conditions are connected. She also donated her brain following her death.
Post-mortem tests revealed significant Alzheimer’s markers, despite years of clinical assessments showing she was cognitively stable.
In fact, she continued to cook, shop and socialize with no noticeable changes in behavior prior to her death.
“Before she passed away, all the clinical assessments in our years of studying her indicated that she was cognitively stable, which is why this case is so fascinating,” said Jr-Jiun Liou, a consortium investigator and neurologist with the University of Pittsburgh.
“Despite her brain’s pathology indicating Alzheimer’s, we think that her cognitive stability could have been attributed to her high education level or underlying genetic factors,” Liou added.
Researchers say the case study could provide game-changing insights into how genetics and lifestyle help some stay sharp despite brain degeneration, potentially offering benefits for the wider population.
“If we can identify the genetic underpinnings or lifestyle factors that allowed her brain to function well despite the pathology, we may uncover strategies that could benefit others,” said Elizabeth Head, a neuroscientist at the University of California, Irvine, and co-author of the study.
People with Down syndrome face a much higher risk of developing Alzheimer’s-related dementia as they age — an estimated three to five times higher than the general population.
Scientists are still working to pinpoint the exact cause, but it’s believed that the extra copy of chromosome 21 drives the overproduction of amyloid precursor protein. This excess production leads to the buildup of amyloid beta plaques in the brain, a hallmark of Alzheimer’s disease.
“Most people with Down syndrome, who have a genetic form of Alzheimer’s, develop learning and memory problems by their mid-50s along with brain changes of Alzheimer’s disease by the time they are in their 40s,” Head told Newsweek.
So what made this woman different? Researchers have several theories.
The patient had a below-average IQ, but she’d received a private education for people with intellectual disabilities. The researchers noted that people with higher levels of education tend to exhibit less cognitive impairment, possibly due to healthier lifestyle choices.
There were also physiological factors that may have given her brain some resistance to Alzheimer’s degeneration, like extra brain tissue or genes that help cope with the buildup of damaged proteins.
The conditions of her Down syndrome may also be a factor. While Down syndrome is characterized by trisomy — having an extra chromosome — some people with it also have mosaicism, in which some cells have three of chromosome 21 but others only have the typical two.
If that were the case with this patient, the uneven spread of the third chromosome might explain her resilience.
Researchers said they hope the case will lead to better diagnostic tools and expand the criteria for clinical trials targeting Alzheimer’s and dementia.
“This study shows how just one person’s participation in research can lead to profound discoveries,” Head said.
