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(American Journal of Pathology. 2001;159:439-447.)
© 2001 American Society for Investigative Pathology

Short Communications

Immunization with a Nontoxic/Nonfibrillar Amyloid-ß Homologous Peptide Reduces Alzheimer’s Disease-Associated Pathology in Transgenic Mice

Einar M. Sigurdsson*{dagger}, Henrieta Scholtzova*, Pankaj D. Mehta{ddagger}, Blas Frangione{dagger}§ and Thomas Wisniewski*{dagger}§

From the Departments of Neurology,*
Pathology,{dagger}
and Psychiatry,§
New York University School of Medicine, New York; and the New York State Institute for Basic Research in Developmental Disabilities,{ddagger}
Staten Island, New York

Transgenic mice with brain amyloid-ß (Aß) plaques immunized with aggregated Aß1-42 have reduced cerebral amyloid burden. However, the use of Aß1-42 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 Aß 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 Aß1-42 were reduced by 57% (P = 0.0019). Ramified microglia expressing interleukin-1ß associated with the Aß plaques were absent in the immunized mice indicating reduced inflammation in these animals. These promising findings suggest that immunization with nonamyloidogenic Aß derivatives represents a potentially safer therapeutic approach to reduce amyloid burden in Alzheimer’s disease, instead of using toxic Aß fibrils.




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