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Oral vaccination with a viral vector containing Aβ cDNA attenuates age‐related Aβ accumulation and memory deficits without causing inflammation in a mouse Alzheimer model
Author(s) -
Mouri Akihiro,
Noda Yukihiro,
Hara Hideo,
Mizoguchi Hiroyuki,
Tabira Takeshi,
Nabeshima Toshitaka
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7685com
Subject(s) - medicine , vaccination , morris water navigation task , immunology , genetically modified mouse , immunotherapy , h&e stain , inflammation , pathology , transgene , immune system , immunohistochemistry , hippocampus , biology , biochemistry , gene
Immunotherapy with Aβ is expected to bring great improvement for Alzheimer disease (AD). However, clinical trials have been suspended because of meningoencephalitics, which accompanied lympho‐cytic infiltration. We have developed an oral vaccine for AD with a recombinant adeno‐associated viral vector carrying Aβ cDNA (AAV/Aβ). The vaccine reduces the amount of Aβ deposited without lymphocytic infiltration in APP transgenic (Tg2576) mice. In the present study, Tg2576 mice showed progressive cognitive impairments in the novel object recognition test, Y‐maze test, water maze test, and contextual conditioned fear learning test. A single oral administration of AAV/Aβ to Tg2576 mice at the age of 10 months alleviated progressive cognitive impairment with decreased Aβ deposition, insoluble Aβ, soluble Aβ oligomer (Aβ*56), microglial attraction, and synaptic degeneration induced in the brain regions at the age of 13 months. A histological analysis with hematoxylin and eosin and an immunohistochemical analysis with antibodies against CD3, CD4, CD8, and CD19 suggested there was no lymphocytic infiltration or microhemorrhage in the brain of AAV/Aβ‐vaccinated Tg2576 mice at 13 months of age. Taken together, these results suggest that immunotherapy with AAV/Aβ is a safe and effective treatment for AD.–Mouri, A., Noda, Y., Hara, H., Mizoguchi, H., Tabira, T., Nabeshima, T. Oral vaccination with a viral vector containing Aβ cDNA attenuates age‐related Aβ accumulation and memory deficits without causing inflammation in a mouse Alzheimer model. FASEB J. 21, 2135–2148 (2007)