Research Roundup - June 2025

Read the below Research Roundup from Penn FTD Center Postdoctoral Fellow Rory Boyle PhD.

Terms to Know:

Trisomy 21: Genetic condition, known as Down syndrome, that occurs were a person has three copies of chromosome 21, instead of the usual two copies.

Amyloid-beta: a toxic protein that is found in the brains of Alzheimer’s disease patients.

APP gene: the amyloid-beta precursor protein gene that is located on chromosome 21. This gene increases production of amyloid-beta and people with Down syndrome have three copies of this gene.

Resistance: less-than-expected pathology at a given level of disease risk. Factors associated with resistance may help to halt or slow the development of Alzheimer’s disease pathological processes.

Resilience: cognitive or functional performance that is better-than-expected at a given level of pathology. Factors associated with resilience may help to reduce or delay the clinical expression of Alzheimer’s disease.

What we knew:

People with Down syndrome have a 90% lifetime prevalence of Alzheimer’s disease and Alzheimer’s disease features emerge earlier in the lifespan of adults with Down syndrome, with the average age at dementia onset of 53.8 years old. In the broader population of adults with Alzheimer’s disease, some individuals show resistance (i.e. reduced development of pathology despite disease risk) and resilience (i.e. better-than-expected cognitive performance despite pathology) to Alzheimer’s disease, which helps to delay the progression of Alzheimer’s disease and mitigate the effects on cognitive function.

What we didn’t know:

We proposed definitions and ways that researchers can study resistance and resilience to Alzheimer’s disease in people with Down syndrome. To understand if there is evidence for resistance and resilience in Down syndrome, we examined variability in the timing of Alzheimer’s disease pathology and symptoms reported in studies of adults with Down syndrome. We then aimed to identify different genetic, biological, socio-behavioral, lifestyle and environmental factors that could be related to this variability and therefore have the potential to support resistance and resilience.

What this research/study shows:

We identified evidence that some people with Down syndrome display based on an absence of abnormal levels of pathology in their 40s. We also found evidence that some people show resilience as there was a substantial proportion of adults with Down syndrome who remained cognitively stable in their 60s and also a subset who remained cognitively stable despite having high levels of Alzheimer’s disease neuropathology when examined post-mortem. We proposed a number of potential factors that could be related to both resistance and resilience and outlined a framework for studying these factors in adults with Down syndrome and Alzheimer’s disease.

What to do with this information:

Given that in Down syndrome development of Alzheimer’s disease pathology is virtually universal, resistance to Alzheimer’s disease in adults with Down syndrome can be considered the absence or reduced levels of AD pathology relative to similar-aged adults with Down syndrome. Resilience can be considered as better-than-expected cognitive performance at a given level of Alzheimer’s disease pathology relative to adults with Down syndrome of a similar age and premorbid intellectual disability level.

More Information:

This study is available here.