PSEN1 and Mental deterioration: The two studies were initiated by the clinical observation of an APOE3Ch carrier having remarkable resistance to amyloid-associated tau pathology and cognitive decline in a known familial AD (FAD) PSEN1 E280A Colombian kindred.3 In the first study, Nelson et al.1 investigated the neuroprotection of the R136S mutation in the context of the common APOE4-related late-onset AD (LOAD), though the clinical benefits in the resilient APOE3Ch carrier were found to be against early-onset AD (EOAD) caused by PSEN1-E280A mutation.