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Passive Immunization against Pyroglutamate-3 Amyloid-β Reduces Plaque Burden in Alzheimer-Like Transgenic Mice: A Pilot Study

Frost J.L.a · Liu B.a · Kleinschmidt M.b · Schilling S.b · Demuth H.-U.b · Lemere C.A.a

Author affiliations

aCenter for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass., USA; bProbiodrug AG, Halle (Saale), Germany

Corresponding Author

Cynthia A. Lemere, PhD

NRB 636F

77 Avenue Louis Pasteur

Boston, MA 02115 (USA)

Tel. +1 617 525 5214, E-Mail clemere@rics.bwh.harvard.edu

Related Articles for ""

Neurodegenerative Dis 2012;10:265–270

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Background: N-terminally truncated and modified pyroglutamate-3 amyloid-β protein (pE3-Aβ) is present in most, if not all, cerebral plaque and vascular amyloid deposits in human Alzheimer’s disease (AD). pE3-Aβ deposition is also found in AD-like transgenic (tg) mouse brain, albeit in lesser quantities than general Aβ. pE3-Aβ resists degradation, is neurotoxic, and may act as a seed for Aβ aggregation. Objective: We sought to determine if pE3-Aβ removal by passive immunization with a highly specific monoclonal antibody (mAb) impacts pathogenesis in a mouse model of Alzheimer’s amyloidosis. Methods: APPswe/PS1ΔE9 tg mice were given weekly intraperitoneal injections of a new anti-pE3-Aβ mAb (mAb07/1) or PBS from 5.8 to 13.8 months of age (prevention) or from 23 to 24.7 months of age (therapeutic). Multiple forms of cerebral Aβ were quantified pathologically and biochemically. Gliosis and microhemorrhage were examined. Results: Chronic passive immunization with an anti-pE3-Aβ mAb significantly reduced total plaque deposition and appeared to lower gliosis in the hippocampus and cerebellum in both the prevention and therapeutic studies. Insoluble Aβ levels in hemibrain homogenates were not significantly different between immunized and control mice. Microhemorrhage was not observed with anti-pE3-Aβ immunotherapy. Conclusions: Selective removal of pE3-Aβ lowered general Aβ plaque deposition suggesting a pro-aggregation or seeding role for pE3-Aβ.

© 2012 S. Karger AG, Basel

Article / Publication Details

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Abstract of Paper

Received: September 15, 2011
Accepted: December 18, 2011
Published online: February 16, 2012
Issue release date: April 2012

Number of Print Pages: 6
Number of Figures: 3
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD

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