Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice.
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.
Sigurdsson
E M
EM
Department of Neurology, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA. einar.sigurdsson@med.nyu.edu
Scholtzova
H
H
Mehta
P D
PD
Frangione
B
B
Wisniewski
T
T
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
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D010446:Peptide Fragments