In vivo reversal of amyloid-beta lesions in rat brain

Cerebral amyloid-beta (A beta) deposition is central to the neuropathologic al definition of Alzheimer disease (AD) with A beta related toxicity being linked to its beta-sheet conformation and/or aggregation. We show that a be ta-sheet breaker peptide (iA beta 5) dose-dependently and reproducibly indu ced in vivo disassembly of fibrillar amyloid deposits, with control peptide s having no effect. The iA beta 5-induced disassembly prevented and/or reve rsed neuronal shrinkage caused by A beta and reduced the extent of interleu kin-1 beta positive microglia-like cells that surround the A beta deposits. These findings suggest that beta-sheet breakers, such as iA beta 5 or simi lar peptidomimetic compounds, may be useful for reducing the size and/or nu mber of cerebral amyloid plaques in A beta, and subsequently diminishing A beta-related histopathology.