A scientific story that began with a discovery in just one extraordinary patient is now panning out. In 2019, an international team that included researchers from two Mass General Brigham hospitals -; Mass Eye and Ear and Massachusetts General Hospital (MGH)-; reported on the case of a patient who did not develop cognitive impairment until her late 70s, despite being part of a family at extremely high genetic risk for developing early-onset Alzheimer's disease. In addition to having the genetic variant that causes an autosomal dominant form of Alzheimer's disease, the woman had two copies of a rare variant of the APOE3 gene, called Christchurch (APOE3Ch).
Now, the research team reports on an additional 27 members of the family who carry just one copy of the variant and experienced delayed disease onset. The study, published in The New England Journal of Medicine, represents the first evidence that having one copy of the Christchurch variant may confer some level of protection against autosomal dominant Alzheimer's disease, even if less pronounced compared to when two copies are present. The findings have important implications for drug development, suggesting the potential effects of targeting this genetic pathway.
As a clinician, I am highly encouraged by our findings, as they suggest the potential for delaying cognitive decline and dementia in older individuals. Now we must leverage this new knowledge to develop effective treatments for dementia prevention. As a neuroscient.