The case of an asymptomatic Alzheimer’s mutation carrier

Interviewer: Joining us today is Dr. Jorge Llibre, a neurologist at Washington University who recently published a Nature Medicine paper reporting the unique case of a person with a high-risk Alzheimer's gene who stayed cognitively healthy for nearly two decades beyond the expected age of onset. Jorge, first of all, thank you very much for joining us today. Dr. Llibre-Guerra: Thanks a lot for the invitation. I'm really happy to join you here and discuss the relevance of this case for the Alzheimer's disease field. Interviewer: It's our pleasure. So to start off, can you describe the resilience case reported in this paper and what makes it so unique? Dr. Llibre-Guerra: I will start by talking about dominant-inherited Alzheimer's disease, and what it means to carry one of these genes. If you carry one of these genes, there is almost 100% penetrance, meaning that people carrying this gene will develop the disease, usually at a really early age. Usually mid-40s, 30s people will start showing symptoms of Alzheimer's disease. What is unique about this individual is that despite carrying a mutation in the PSEN1 gene, he has remained cognitively healthy for 20 years over the expected age of onset. At the same time, when we take a look at the neuroimaging findings of this individual, similar to other mutation carriers, the individual has a lot of amyloid deposition, so a high burden of amyloid throughout the brain, but different from other individuals tau pathology is only restricted to one specific area of the brain, which is the left occipital cortex. Now, I have to mention this is not the only individual with dominant-inherited Alzheimer's disease that is not showing symptoms. There have been two other cases reported in Colombia,