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Augustine Chemparathy, et al. – Stanford University.
In this study, 6 subjects carrying highly rare APOE loss-of-function (LoF) variants showed resilience to AD pathology. This resilience ranged from delayed impairment to remaining cognitively healthy & free of amyloid at death despite reaching age 90+. These results suggest that the risks from APOE4 are due to toxic gain-of-function, rather than LoF, and that therapeutic knock-down of APOE4 would be beneficial & well-tolerated.