Active vaccination with ankyrin G reduces β-amyloid pathology in APP transgenic mice

Mol Psychiatry. 2013 Mar;18(3):358-68. doi: 10.1038/mp.2012.70. Epub 2012 Jun 12.


Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in β-amyloid plaques. Active immunization with ankG of arcAβ transgenic mice reduced brain β-amyloid pathology and increased brain levels of soluble Aβ(42). AnkG immunization induced a reduction in β-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aβ-induced loss of dendritic spines in hippocampal ArcAβ organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain β-amyloid and its related neuropathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Ankyrins / immunology*
  • Ankyrins / metabolism
  • Antibodies / blood
  • Antibodies, Monoclonal / pharmacology
  • Brain / metabolism
  • Brain / pathology*
  • Cells, Cultured
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Humans
  • Mice
  • Mice, Transgenic
  • Neurons / cytology
  • Peptide Fragments / metabolism
  • Plaque, Amyloid / metabolism
  • Vaccination*


  • ANK3 protein, human
  • Amyloid beta-Peptides
  • Ankyrins
  • Antibodies
  • Antibodies, Monoclonal
  • Peptide Fragments
  • amyloid beta-protein (1-42)