Research often feels incremental, building slowly on studies of large cohorts of people over long periods of time who enable scientists to answer critical questions with a high degree of precision needed to detect meaningful, if small, differences between groups. But every once in a while, even a single research volunteer can empower science to move faster, changing the way we think about disease mechanisms or opportunities for treatment. Alzheimer’s disease research includes many such cases. They include people with early onset of Alzheimer’s disease that helped us understand genetic causes of the disease, who also taught us much about the biology of the disease such as amyloid beta processing and disease progression. Other cases revealed remarkable protection from this genetic fate, due to other gene mutations, such as person from the Colombian kindred carrying the so-called Christchurch mutation who lived well beyond the expected time of dementia onset predicted by this familial mutation.
Here at UCI MIND, in the Center for Aging Research-Down Syndrome and as part of the NIH-funded Alzheimer’s Disease Research Center and the NIH-funded Alzheimer Biomarker Consortium – Down syndrome (ABC-DS) Study, we recently described a remarkable case of a 63 year old woman with Down syndrome who was similarly resilient to a presumed predetermined fate. People with Down syndrome carry an extra copy of the 21st chromosome and the APP gene is on this chromosome. This extra copy of this gene nearly always leads to people with Down syndrome developing the plaques and tangles of Alzheimer’s disease by age 40 years, with cognitive decline occurring almost a decade later.
As we described in a recent paper that was covered by Newsweek. This amazing volunteer in our study, who contributed more than 30-years of data(!!) and gave the gift of brain donation, demonstrated resistance to Alzheimer disease. She lived into her 60s with relatively stable cognition well past the time when most people with Down syndrome show signs of dementia, which we call resilience. She also showed lower brain changes associated with Alzheimer disease than what we may also predict for a person with Down syndrome of her age. Our research participant had more and better education than is typical, she carried the e2 allele of the APOE gene, and had a larger than average brain. Either some or all of these factors, and other potential explanations may have contributed to her highly unique clinical course. We continue to explore these possibilities, in hopes of identifying novel ways to deliver resilience and resistance to all people at risk for Alzheimer’s disease with and without Down syndrome as well as other causes of dementia. Research volunteers like this single person and funding from the NIH are essential to our eventual success.
