Chapter 1 Amyloid and Amyloid-Like Protein Aggregates in Neurodegenerative Disease

Abstract

The chapter presents a study on amyloid and amyloid-like protein aggregates in neurodegenerative disease. The term “amyloid” refers to the quaternary structure of a protein deposit. The molecular arrangement in amyloid allows for hydrogen bonding between the amino acids on opposing peptide strands and results in amyloids producing a characteristic X-ray diffraction pattern. A number of diseases collectively labeled the “amyloidoses” are associated with amyloid deposits. Although this chapter focuses only on amyloid deposits and protein aggregates that directly affect CNS function, the systemic amyloid deposition is associated with more than 20 different diseases, including common systemic disorders such as type II diabetes. Most amyloid deposits are initially identified in situ through the use of particular dyes (for example, Congo red or thioflavin S/T) that bind amyloid irrespective of the primary sequence of the peptide or protein within the deposit. There is evidence supporting the concept that amyloid formation is a concentration-dependent phenomenon that is initiated via a seeded polymerization reaction. The strongest evidence that the process of amyloid formation is linked to neurodegeneration has come from the study of genetic mutations that cause early-onset autosomal dominant familial forms of Alzheimer's disease (FAD), BFD, and familial Danish dementia (FDD). One remarkable hallmark of all extracellular amyloids is the presence of certain cofactors that are almost invariably codeposited as a nonfibrillar component of the plaque.