title: Immunomodulation targeting of both Aβ and tau pathological conformers ameliorates Alzheimer's disease pathology in TgSwDI and 3xTg mouse models.
abstract: BACKGROUND
  Central to the pathogenesis of Alzheimer's disease (AD) and many other neurodegenerative diseases is the conformational change of a normal self-protein into toxic oligomeric species and amyloid deposits. None of these disorders have an effective therapy, but immunization approaches hold great promise. We have previously shown that active immunization with a novel peptide when polymerized into a stable oligomeric conformation, pBri, induced a humoral immune response to toxic Aβ species in an AD model, APP/PS1 transgenic (Tg) mice, reducing plaque deposits. pBri is a glutaraldehyde polymerized form of the carboxyl fragment of an amyloidogenic protein, which is deposited in the brains of patients with a rare autosomal dominant disease due to a missense mutation in a stop codon, resulting in the translation of an intronic sequence, with no known sequence homology to any mammalian protein.
  
  
  METHODS
  In the current study we tested whether pBri-peptide-based immunomodulation is effective at reducing both vascular amyloid deposits and tau-related pathology using TgSwDI mice with extensive congophilic angiopathy and 3xTg mice with tau pathology.
  
  
  RESULTS
  Our results indicate that this immunomodulation approach, which produces a humoral response to proteins in a pathological conformation, is effective at reducing both Aβ and tau-related pathologies.
  
  
  CONCLUSIONS
  This immunomodulatory approach has the advantage of using a non-self-immunogen that is less likely to be associated with autoimmune toxicity. Furthermore we found that it is able to target all the cardinal features of AD concurrently.
authors: Fernando
authors: F
authors: Goñi
authors: Krystal
authors: K
authors: Herline
authors: Daniel
authors: D
authors: Peyser
authors: Kinlung
authors: K
authors: Wong
authors: Yong
authors: Y
authors: Ji
authors: Yanjie
authors: Y
authors: Sun
authors: Pankaj
authors: P
authors: Mehta
authors: Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. Thomas.wisniewski@nyumc.org.
authors: Thomas
authors: T
authors: Wisniewski
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D058227:Amyloidogenic Proteins / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007114:Immunization; D008163:Luminescent Measurements; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D017433:Protein Structure, Secondary; D016875:tau Proteins / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D058227:Amyloidogenic Proteins; D016875:tau Proteins