Single amino acid change in the receptor binding domain of mouse APOE results in altered protein dynamics and worsened AD‐related cognitive impairment

APOE genotype is the strongest genetic modifier of late‐onset Alzheimer’s disease (AD) in humans. In genetically diverse mice, natural variation in the Apoe locus predicts AD‐related cognitive decline, with C57BL/6J (B6) mice harboring a protective variant compared to DBA/2J (D2) (Neuner 2019, Neuron). The mechanisms by which protective and detrimental Apoe/APOE variants affect cognitive decline in AD are not fully understood yet, but likely could provide an opportunity for personalized treatment and prevention strategies.