Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice

Transgenic mice with brain amyloid-beta (A beta) plaques immunized with agg regated A beta1-42 have reduced cerebral amyloid burden. However, the use o f A beta1-42 in humans may not be appropriate because it crosses the blood brain barrier, forms toxic fibrils, and can seed fibril formation. We repor t that immunization in transgenic APP mice (Tg2576) for 7 months with a sol uble nonamyloidogenic, nontoxic A beta homologous peptide reduced cortical and hippocampal brain amyloid burden by 89% (P = 0.0002) and 81% (P = 0.000 1), respectively. Concurrently, brain levels of soluble A beta1-42 were red uced by 57% (P = 0.0019). Ramified microglia expressing interieukin-1 beta associated with the A beta plaques were absent in the immunized mice indica ting reduced inflammation in these animals. These promising findings sugges t that immunization with nonamyloidogenic A beta derivatives represents a p otentially safer therapeutic approach to reduce amyloid burden in Alzheimer 's disease, instead of using toxic A beta fibrils.