APOE Antibody Inhibits Aβ-Associated Tau Seeding and Spreading in a Mouse Model.

Abstract

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.

• Authors: Maud Gratuze, Hong Jiang, Chanung Wang, Monica Xiong, Xin Bao, David M Holtzman
• Journal: Annals of neurology (Ann Neurol) Vol. 91 Issue 6 Pg. 847-852 (06 2022) ISSN: 1531-8249 [Electronic] United States
• PMID: 35285073 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 American Neurological Association.

Chemical References

• Amyloid beta-Peptides
• Antibodies
• Apolipoprotein E4
• Apolipoproteins E
• tau Proteins

Topics

• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Antibodies
• Apolipoprotein E4 (genetics)
• Apolipoproteins E (genetics)
• Brain (metabolism)
• Disease Models, Animal
• Humans
• Mice
• Mice, Transgenic
• Plaque, Amyloid (metabolism)
• tau Proteins (genetics, metabolism)