MAPT and tauopathy: Genetic evidence suggests that in the CNS, apoE ε4 promotes neurodegeneration through a toxic gain‐of‐function mechanism55, 77, 97 and that removing apoE completely in a mouse model of tauopathy blocks most tau‐mediated neurodegeneration98 and decreasing apoE ε4 in the brain by ∼50% using antisense oligonucleotides also significantly reduces tau‐mediated neurodegeneration.99