Task fMRI activity in an Autosomal Dominant mutation carrier demonstrating extreme resilience

The high levels of amyloid indicate a preserved penetrance of the mutation. The atypical tau pathology, greatly limited spread relative to expected patterns, suggests why overall cognition is preserved. However it is unknown if the cortical areas with high tau are truly resilient to pathology. It is possible that the tissue is impaired, but overt cognitive deficits are undetected due to the unilateral presentation largely limiting impairment to one hemisphere. The analysis of the task fMRI data will directly inform us as to the health of the underlying tissue. This will help differentiate if the resilience is tied to a reduced toxicity or biological resistance to the tau pathology or the reduced spread of pathology. Differentiating these outcomes will be incredibly important to interpreting mechanisms that infer resilience, even with strong genetic drivers of pathology.