title: Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice.
abstract: Transgenic mice with brain amyloid-beta (Abeta) plaques immunized with aggregated Abeta1-42 have reduced cerebral amyloid burden. However, the use of Abeta1-42 in humans may not be appropriate because it crosses the blood brain barrier, forms toxic fibrils, and can seed fibril formation. We report that immunization in transgenic APP mice (Tg2576) for 7 months with a soluble nonamyloidogenic, nontoxic Abeta homologous peptide reduced cortical and hippocampal brain amyloid burden by 89% (P = 0.0002) and 81% (P = 0.0001), respectively. Concurrently, brain levels of soluble Abeta1-42 were reduced by 57% (P = 0.0019). Ramified microglia expressing interleukin-1beta associated with the Abeta plaques were absent in the immunized mice indicating reduced inflammation in these animals. These promising findings suggest that immunization with nonamyloidogenic Abeta derivatives represents a potentially safer therapeutic approach to reduce amyloid burden in Alzheimer's disease, instead of using toxic Abeta fibrils.
authors.affiliation: Department of Neurology, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA. einar.sigurdsson@med.nyu.edu
authors.forename: E M
authors.initials: EM
authors.lastname: Sigurdsson
authors.forename: H
authors.initials: H
authors.lastname: Scholtzova
authors.forename: P D
authors.initials: PD
authors.lastname: Mehta
authors.forename: B
authors.initials: B
authors.lastname: Frangione
authors.forename: T
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D002470:Cell Survival; D002540:Cerebral Cortex / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007114:Immunization; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D010446:Peptide Fragments