Immunization with amyloid-beta attenuates Alzheimer disease-like pathologyin the PDAPP mouse

Amyloid-beta peptide (A beta) seems to have a central role in the neuropath ology of Alzheimer's disease (AD)(1). Familial forms of the disease have be en linked to mutations in the amyloid precursor protein (APP) and the prese nilin genes(2,3). Disease-linked mutations in these genes result in increas ed production of the 42-amino-acid form of the peptide (A beta(42))(4-8), w hich is the predominant form found in the amyloid plaques of Alzheimer's di sease(9,10). The PDAPP transgenic mouse, which overexpresses mutant human A PP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallm arks of Alzheimer's disease in an age- and brain-region-dependent manner(11 ,12). In the present study, transgenic animals were immunized with A beta(4 2), either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several o f the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the developme nt of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. T reatment of the older animals also markedly reduced the extent and progress ion of these AD-like neuropathologies. Our results raise the possibility th at immunization with amyloid-beta may be effective in preventing and treati ng Alzheimer's disease.