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

Abstract

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 genes²,³. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Aβ₄₂)^4,5,6,7,8, which is the predominant form found in the amyloid plaques of Alzheimer's disease⁹,^{& St George-Hyslop, P. Aβ-42 deposition precedes other changes in PS-1 Alzheimer's disease.Lancet 352, 1117–1118 (1998)." href="/articles/22124#ref10" aria-label="Reference 10" data-track="click" data-track-action="reference anchor" data-track-label="link">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 manner¹¹,¹². In the present study, transgenic animals were immunized with Aβ₄₂, 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.