Reaction of Amyloid-β Peptide Antibody with Different Infectious Agents Involved in Alzheimer's Disease

J Alzheimers Dis. 2018;63(2):847-860. doi: 10.3233/JAD-170961.

Abstract

As early as the 1980s, molecular virologist Ruth Itzhaki began to investigate if there was a causal connection between infections and neurodegenerative disorder. Although the theory has yet to be universally embraced, in 2016 Itzhaki and 33 other scientists from all over the world published a review article in this very journal presenting evidence for the causal role of pathogens in Alzheimer's disease (AD). Exactly how and in what way pathogens affect the induction of AD has yet to be determined, but one possible answer may involve the cross-reactivity of different pathogens with amyloid-β (Aβ). Aβ autoantibodies have been detected in the serum and cerebrospinal fluid of AD patients and in some healthy individuals. In the present study our major goal was to investigate whether antibodies made against Aβ would react both with other brain proteins as well as pathogens associated with AD as a result of molecular mimicry or the binding of bacterial toxins to Aβ42. Our study used a specific monoclonal antibody made against Aβ42, which not only reacted strongly with Aβ42, tau protein, and α-synuclein, but also had from weak to strong reactions with 25 different pathogens or their molecules, some of which have been associated with AD. The homology between peptide stretches of microbial origin and proteins involved in AD could be a mechanism by which antibodies to homologous peptides mount attacks against autoantigens in AD. We concluded that bacterial molecules bind to Aβ protein, forming small oligomers, then encasing pathogens and their molecules to form amyloid plaques, the tell-tale markers of AD. Conversely, these same Aβ peptides induce the production of antibodies to both Aβ42 and bacterial molecules, which may inhibit bacterial pathogenesis, but in the process may promote amyloid plaque formation.

Keywords: Alzheimer’s disease; amyloid-β; autoantibody; molecular mimicry; pathogens.

MeSH terms

  • Alzheimer Disease / immunology*
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Bacterial / immunology*
  • Antigens, Viral / immunology*
  • Autoantibodies / immunology*
  • Cross Reactions
  • Humans
  • Mice
  • Molecular Mimicry
  • Peptide Fragments / immunology*
  • Rabbits

Substances

  • Amyloid beta-Peptides
  • Antibodies, Monoclonal
  • Antigens, Bacterial
  • Antigens, Viral
  • Autoantibodies
  • Peptide Fragments
  • amyloid beta-protein (1-42)