title: Passive immunization against pyroglutamate-3 amyloid-β reduces plaque burden in Alzheimer-like transgenic mice: a pilot study.
abstract: 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.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Frost
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Martin
authors.initials: M
authors.lastname: Kleinschmidt
authors.forename: Stephan
authors.initials: S
authors.lastname: Schilling
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000209:etiology / Q000628:therapy; D000818:Animals; D000906:Antibodies / Q000097:blood; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005911:Gliosis / Q000209:etiology / Q000628:therapy; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D010865:Pilot Projects; D058225:Plaque, Amyloid / Q000209:etiology / Q000628:therapy; D053764:Presenilin-1 / Q000235:genetics; D011761:Pyrrolidonecarboxylic Acid / Q000276:immunology*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D011761:Pyrrolidonecarboxylic Acid