PSEN1 and Cognitive impairment: For example, homozygosity of the APOE3 Christchurch mutation has already been suggested to confer resistance to tau pathology in ADAD: a PSEN1 E280A amyloid-positive mutation carrier had both limited and atypical distribution of tau signal on PET scanning despite being over 30 years beyond the median age of onset of mild cognitive impairment [53].