Journal Article

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

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

1999

Overview

Amyloid-β peptide (Aβ) seems to have a central role in the neuropathology of Alzheimer's disease (AD) 1 . Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes 2 , 3 . Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Aβ 42 ) 4 , 5 , 6 , 7 , 8 , which is the predominant form found in the amyloid plaques of Alzheimer's disease 9 , 10 . 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 11 , 12 . In the present study, transgenic animals were immunized with Aβ 42 , either before the onset of AD-type neuropathologies (at 6 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 that 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.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Alzheimer Disease - immunology / Alzheimer Disease - pathology / Alzheimer Disease - prevention & control / Alzheimer's disease / Amino acids / Amyloid beta-Peptides - administration & dosage / Amyloid beta-Peptides - immunology / Amyloid beta-Peptides - metabolism / Animals / Astrocytes - pathology / Biological and medical sciences / Brain - pathology / Buffers / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Dystrophy / Enzyme-Linked Immunosorbent Assay / Freund's Adjuvant - administration & dosage / Genes / Hippocampus - pathology / Humanities and Social Sciences / Humans / Immunity (Disease) / Immunization / letter / Medical sciences / Mice / Mice, Transgenic / multidisciplinary / Mutation / Neurites - pathology / Neurology / Peptide Fragments - administration & dosage / Peptide Fragments - immunology / Peptides / Point Mutation / Proteins / Rodents / Science / Science (multidisciplinary) / Serum Amyloid P-Component - administration & dosage / Serum Amyloid P-Component - immunology / Vaccination