Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis

Jungsu Kim, Adam E M Eltorai, Hong Jiang, Fan Liao, Philip B. Verghese, Jaekwang Kim, Floy R. Stewart, Jacob M. Basak, David M. Holtzman

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The apolipoprotein E (APOE) E{open}4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). The influence of apoE on amyloid β (Aβ) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with Aβ and facilitates Aβ fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-Aβ antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe/PS1ΔE9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60-80% and significantly reduced insoluble Aβ40 and Aβ42 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around Aβ plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in Aβ binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases.

Original languageEnglish (US)
Pages (from-to)2149-2156
Number of pages8
JournalJournal of Experimental Medicine
Volume209
Issue number12
DOIs
StatePublished - Nov 2012
Externally publishedYes

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Apolipoproteins E
Amyloidosis
Amyloid
Immunotherapy
Transgenic Mice
Anti-Idiotypic Antibodies
Alzheimer Disease
Proteins
Proteostasis Deficiencies
Microglia
Immunization
Therapeutics
Alleles
Monoclonal Antibodies
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Kim, J., Eltorai, A. E. M., Jiang, H., Liao, F., Verghese, P. B., Kim, J., ... Holtzman, D. M. (2012). Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis. Journal of Experimental Medicine, 209(12), 2149-2156. https://doi.org/10.1084/jem.20121274

Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis. / Kim, Jungsu; Eltorai, Adam E M; Jiang, Hong; Liao, Fan; Verghese, Philip B.; Kim, Jaekwang; Stewart, Floy R.; Basak, Jacob M.; Holtzman, David M.

In: Journal of Experimental Medicine, Vol. 209, No. 12, 11.2012, p. 2149-2156.

Research output: Contribution to journalArticle

Kim, J, Eltorai, AEM, Jiang, H, Liao, F, Verghese, PB, Kim, J, Stewart, FR, Basak, JM & Holtzman, DM 2012, 'Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis', Journal of Experimental Medicine, vol. 209, no. 12, pp. 2149-2156. https://doi.org/10.1084/jem.20121274
Kim, Jungsu ; Eltorai, Adam E M ; Jiang, Hong ; Liao, Fan ; Verghese, Philip B. ; Kim, Jaekwang ; Stewart, Floy R. ; Basak, Jacob M. ; Holtzman, David M. / Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 12. pp. 2149-2156.
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