Immunization with amyloid-β attenuates Alzheimer disease-like pathology in the PDAPP mouse

Dale Schenk, Robin Barbour, Whitney Dunn, Grace Gordon, Henry Grajeda, Teresa Guldo, Kang Hu, Jiping Huang, Kelly Johnson-Wood, Karen Khan, Dora Kholodenko, Mike Lee, Zhenmei Liao, Ivan Lieberburg, Ruth Motter, Linda Mutter, Ferdie Soriano, George Shopp, Nicki Vasquez, Christopher VandevertShannan Walker, Mark Wogulis, Ted Yednock, Dora Games, Peter Seubert

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Abstract

Amyloid-β peptide (Aβ) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Aβ42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Aβ42, either before the onset of AD-type neuropathologies (at 5 weeks of age) or at an older age (11 months), when amyloid-β deposition and several of the subsequent neuropathological changes were well established. We report the immunization of the young animals essentially prevented the development of β-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-β may be effective in preventing and treating Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)173-177
Number of pages5
JournalNature
Volume400
Issue number6740
DOIs
StatePublished - Jul 8 1999
Externally publishedYes

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Cite this

Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guldo, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., ... Seubert, P. (1999). Immunization with amyloid-β attenuates Alzheimer disease-like pathology in the PDAPP mouse. Nature, 400(6740), 173-177. https://doi.org/10.1038/22124