LAUSR

APOE is the strongest genetic factor for late‐onset Alzheimer's disease (AD). A specific conformation of the ApoE protein is present in amyloid‐β (Aβ) containing plaques. Immunotherapy targeting ApoE in plaques reduces brain Aβ deposits in mice. Here, we evaluated the effects of the anti‐human APOE antibody HAE‐4 on amyloid plaques, Aβ‐mediated tau seeding and spreading, and neuritic dystrophy in the 5XFAD amyloid mice expressing human ApoE4. HAE‐4 reduced Aβ plaques as well as Aβ‐driven tau seeding/spreading and neuritic dystrophy. These results demonstrate that HAE‐4 may provide therapeutic effects on amyloid removal and Aβ driven downstream consequences such as tauopathy. ANN NEUROL 2022;91:847–852