Anti-ApoE antibody given after plaque onset decreases Aβ accumulation and improves brain function in a mouse model of Aβ amyloidosis

Fan Liao, Yukiko Hori, Eloise Hudry, Adam Q. Bauer, Hong Jiang, Thomas E. Mahan, Katheryn B. Lefton, Tony J. Zhang, Joshua T. Dearborn, Jungsu Kim, Joseph P. Culver, Rebecca Betensky, David F. Wozniak, Bradley T. Hyman, David M. Holtzman

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Apolipoprotein E (apoE) is the strongest known genetic risk factor for late onset Alzheimer's disease (AD). It influences amyloid-β (Aβ) clearance and aggregation, which likely contributes in large part to its role in AD pathogenesis. We recently found that HJ6.3, a monoclonal antibody against apoE, significantly reduced Aβ plaque load when given to APPswe/PS1 ΔE9 (APP/PS1) mice starting before the onset of plaque deposition. To determine whether the anti-apoE antibody HJ6.3 affects Aβ plaques, neuronal network function, and behavior in APP/PS1 mice after plaque onset, we administered HJ6.3 (10 mg/kg/week) or PBS intraperitoneally to 7-month-old APP/PS1 mice for 21 weeks. HJ6.3 mildly improved spatial learning performance in the water maze, restored resting-state functional connectivity, and modestly reduced brain Aβ plaque load. There was no effect of HJ6.3 on total plasma cholesterol or cerebral amyloid angiopathy. To investigate the underlying mechanisms of anti-apoE immunotherapy, HJ6.3 was applied to the brain cortical surface and amyloid deposition was followed over 2 weeks using in vivo imaging. Acute exposure to HJ6.3 affected the course of amyloid deposition in that it prevented the formation of new amyloid deposits, limited their growth, and was associated with occasional clearance of plaques, a process likely associated with direct binding to amyloid aggregates. Topical application of HJ6.3 for only 14 d also decreased the density of amyloid plaques assessed postmortem. Collectively, these studies suggest that anti-apoE antibodies have therapeutic potential when given before or after the onset of Aβ pathology.

Original languageEnglish (US)
Pages (from-to)7281-7292
Number of pages12
JournalJournal of Neuroscience
Volume34
Issue number21
DOIs
StatePublished - 2014

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Apolipoproteins E
Amyloidosis
Anti-Idiotypic Antibodies
Amyloid
Brain
Amyloid Plaques
Alzheimer Disease
Cerebral Amyloid Angiopathy
Antibodies
Immunotherapy
Cholesterol
Monoclonal Antibodies
Pathology
Water
Growth

Keywords

  • Alzheimer's
  • Amyloid
  • Antibody
  • Apolipoprotein E

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Anti-ApoE antibody given after plaque onset decreases Aβ accumulation and improves brain function in a mouse model of Aβ amyloidosis. / Liao, Fan; Hori, Yukiko; Hudry, Eloise; Bauer, Adam Q.; Jiang, Hong; Mahan, Thomas E.; Lefton, Katheryn B.; Zhang, Tony J.; Dearborn, Joshua T.; Kim, Jungsu; Culver, Joseph P.; Betensky, Rebecca; Wozniak, David F.; Hyman, Bradley T.; Holtzman, David M.

In: Journal of Neuroscience, Vol. 34, No. 21, 2014, p. 7281-7292.

Research output: Contribution to journalArticle

Liao, F, Hori, Y, Hudry, E, Bauer, AQ, Jiang, H, Mahan, TE, Lefton, KB, Zhang, TJ, Dearborn, JT, Kim, J, Culver, JP, Betensky, R, Wozniak, DF, Hyman, BT & Holtzman, DM 2014, 'Anti-ApoE antibody given after plaque onset decreases Aβ accumulation and improves brain function in a mouse model of Aβ amyloidosis', Journal of Neuroscience, vol. 34, no. 21, pp. 7281-7292. https://doi.org/10.1523/JNEUROSCI.0646-14.2014
Liao, Fan ; Hori, Yukiko ; Hudry, Eloise ; Bauer, Adam Q. ; Jiang, Hong ; Mahan, Thomas E. ; Lefton, Katheryn B. ; Zhang, Tony J. ; Dearborn, Joshua T. ; Kim, Jungsu ; Culver, Joseph P. ; Betensky, Rebecca ; Wozniak, David F. ; Hyman, Bradley T. ; Holtzman, David M. / Anti-ApoE antibody given after plaque onset decreases Aβ accumulation and improves brain function in a mouse model of Aβ amyloidosis. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 21. pp. 7281-7292.
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AU - Lefton, Katheryn B.

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