A noninflammatory immune response in aged DNA Aβ42-immunized mice supports its safety for possible use as immunotherapy in AD patients

Neurobiol Aging. 2015 Mar;36(3):1274-81. doi: 10.1016/j.neurobiolaging.2014.12.011. Epub 2014 Dec 12.


Aging in the immune system results in tendency to proinflammatory responses. Intradermal DNA immunization showed Th2 polarized noninflammatory immune responses. We tested here 18-month-old mice which were immunized with Aβ42 peptide, DNA Aβ42 trimer, or 2 different prime boost protocols identical to previous experiments. High Aβ42 antibody levels were found in aged mice which had received peptide immunizations (900 μg/mL plasma), and in mice which had received peptide prime and DNA boost immunizations (500 μg/mL), compared with antibodies in DNA Aβ42 immunized mice with 50 μg/mL. Although we found T-cell proliferation and inflammatory cytokines in mice which had received peptide or prime boost immunization, these were not found in DNA-immunized mice. The results are concordant with proinflammatory responses because of immunosenescence and contraindicate the use of Aβ42 peptide immunizations or prime boost immunization protocols for the use in elderly Alzheimer's disease patients. DNA Aβ42 immunization only on the other hand does lead to effective levels of antibodies without inflammatory cytokine or T-cell responses in the aged animal model tested.

Keywords: Aging; Alzheimer disease; Aβ42 immunotherapy; Immunosenescence; Inflammaging; Inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / immunology*
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Antibodies / blood
  • DNA / immunology*
  • Disease Models, Animal
  • Immunotherapy / methods*
  • Inflammation Mediators / blood
  • Mice, Inbred Strains
  • Peptide Fragments / immunology*
  • T-Lymphocytes / immunology


  • Amyloid beta-Peptides
  • Antibodies
  • Inflammation Mediators
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • DNA