As research has shown that people with Down syndrome (DS) have over a 90 per cent lifetime risk of developing dementia caused by Alzheimer’s disease (AD) as they age, researchers have set out to uncover why some people with DS develop dementia while others do not.
A case study has found an unexpected Alzheimer’s disease progression in an woman with Down syndrome. For ten years, a woman with Down syndrome participated in the Alzheimer Biomarker Consortium – Down syndrome Research Study (ABC-DS).
At the time of her passing, investigators were grateful for her gift of brain donation, and her brain was shared with the University of Pittsburgh’s 7T Bioengineering Research Program radiofrequency research facility, where her brain was imaged using the team’s high-resolution 7 Tesla MRI scanner.
“We are interested in trying to link neuroimaging with neuropathology, because we want to use information from neuropathology datasets to inform diagnostic and therapeutic criteria for individuals with Down syndrome before they pass away,” said Jr-Jiun Liou, postdoctoral scholar in the department of bioengineering.
The final neuroimages revealed surprising findings. Although the participant was cognitively stable at the time of death, MRI imaging revealed the presence of neuropathology indicative of Alzheimer’s disease in her brain. This finding highlighted a discrepancy between her lived experience and clinical diagnosis compared to her underlying biological pathology.
“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,” Liou said.
“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 and Head hope that this case study will help improve existing diagnostic tools and expand the inclusion criteria for therapeutic drug trials targeting Alzheimer’s disease and dementia. Clinical trials typically have narrow criteria for acceptance, but if more individuals with this type of “hidden” pathology for Alzheimer’s are included, the treatments could become more effective.
The data also presents a rare opportunity to uncover genetic or lifestyle factors that may contribute to cognitive preservation—insights that could ultimately benefit not only individuals with Down syndrome but the broader 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,” Head said. “This study shows how just one person’s participation in research can lead to profound discoveries.”
