Chapter 3. β-Amyloid as a Target for Alzheimer's Disease Therapy

Publisher Summary This chapter analyzes β-amyloid as a target for Alzheimer's disease (AD) therapy. One of the cardinal pathological signatures of AD is the deposition of the β-amyloid (Aβ) peptide in the cores of senile plaques and in the walls of cerebral blood vessels. This 39-42 amino acid peptide is formed from the cleavage of a larger species, the β-amyloid precursor protein (βAPP), and is prone to self-aggregation. The Aβ peptide plays a key role in the pathogenesis of AD. One approach for blocking the formation of β-amyloid is to inhibit the polymerization of this peptide. For other amyloidoses, such as AA and AL amyloidosis, it has been shown that blocking or removing the amyloidogenic peptide, can reverse the process. This chapter discusses the search for amyloid fibrillization inhibitors. Use of techniques, such as electron microscopy, X-ray diffraction, atomic force microscopy (AFM), light scattering, fluorescence, nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR) for analysis of amyloids is discussed. An overview of β-amyloid inhibitors is presented and inhibition of Aβ toxicity is also discussed in the chapter.