Inhibition of Alzheimer's disease β‐amyloid aggregation, neurotoxicity, and <i>in vivo</i> deposition by nitrophenols: implications for Alzheimer's therapy

Abstract

ABSTRACT Alzheimer's disease (AD) is a major public health problem, and there is currently no clinically accepted treatment to cure it or to stop its progression. Fibrillar aggregates of the β–amyloid peptide (Aβ) are major constituents of the senile plaques found in the brains of AD patients and have been related to AD neurotoxicity. Here it is shown that nitrophenols prevent aggregation and cause disaggregation of Aβ fibrils and that they strongly prevent the neurotoxicity of Aβ to rat hippocampal neurons in culture. Furthermore, by using an in vivo model system of cerebral amyloid deposition, it is shown that nitrophenols cause a marked reduction in the volume occupied by amyloid deposits in the hippocampi of rats. These results raise the possibility that nitrophenols or their derivatives may be useful lead compounds for the development of drugs to prevent the neurotoxicity and deposition of Aβ in AD.