Intranasal Aβ Vaccination as an Approach to Treating β-Amyloidosis

  • D. J. Selkoe
Conference paper
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)


The cerebral accumulation of amyloid β-protein (AP) in Alzheimer’s disease (AD) is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis and the release of pro-inflammatory cytokines and acute phase proteins. Mucosal administration of disease-implicated proteins can induce antigen-specific, anti-inflammatory immune responses in mucosal lymphoid tissue which subsequently act systemically. We hypothesized that chronic mucosal administration of Aβ peptide might induce an anti-inflammatory immune process in which cells induced in the mucosa would circulate to and enter brain tissue to provide a Th2-type cytokine response that could decrease local inflammation. To test this hypothesis, we treated human APP transgenic mice between the ages of ~5 and ~12 months with synthetic human Aβ1–40 peptide given mucosally (orally or intranasally) each week. In the mice treated intranasally, we found significant decreases in cerebral Aβ plaque burden as well as Aβ42 levels, compared to a control group of mice treated with myelin basic protein or left untreated. The lower Aβ burden in the nasally treated mice was associated with decreased local microglial and astrocytic activation, decreased neuritic dystrophy, serum anti-Aβ antibodies of the IgGl and IgG2b classes and a small number of mononuclear cells in the brain expressing the anti-inflammatory cytokines, IL-4, IL-10 and TGF-β. Our results demonstrate that chronic nasal administration of Aβ can induce a cellular and humoral immune response to Aβ that decreases cerebral Aβ levels, suggesting a novel mucosal immunological approach for the treatment and prevention of AD.


Experimental Autoimmune Encephalomyelitis Myelin Basic Protein Plaque Burden Neuritic Dystrophy Nasal Administration 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • D. J. Selkoe
    • 1
  1. 1.Center for Neurologic DiseasesHarvard Medical School and Brigham and Women’s HospitalBostonUSA

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