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

NEUROBIOLOGY OF AGING

卷:36

Article

Lambracht-Washington, Doris¹  Rosenberg, Roger N.¹ 

[1] Univ Texas SW Med Ctr Dallas, Alzheimers Dis Ctr, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA

关键词: Alzheimer disease;    Aging;    A beta 42 immunotherapy;    Inflammation;    Immunosenescence;    Inflammaging;   

DOI  :  10.1016/j.neurobiolaging.2014.12.011

来源: Elsevier

【 摘 要 】

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 A beta 42 peptide, DNA A beta 42 trimer, or 2 different prime boost protocols identical to previous experiments. High A beta 42 antibody levels were found in aged mice which had received peptide immunizations (900 mu g/mL plasma), and in mice which had received peptide prime and DNA boost immunizations (500 mu g/mL), compared with antibodies in DNA A beta 42 immunized mice with 50 mu g/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 A beta 42 peptide immunizations or prime boost immunization protocols for the use in elderly Alzheimer's disease patients. DNA A beta 42 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. (C) 2015 Elsevier Inc. All rights reserved.

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