Aggregation and structure of amyloid ß-protein.

ABSTRACT

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by major pathological hallmarks in the brain, including plaques composed of amyloid ß-protein (Aß) and neurofibrillary tangles of tau protein. Genetic studies, biochemical data, and animal models have suggested that Aß is a critical species in the pathogenesis of AD. Aß molecules aggregate to form oligomers, protofibrils (PFs), and mature fibrils. Because of their instability and structural heterogeneity, the misfolding and aggregation of Aß is a highly complex process, leading to a variety of aggregates with different structures and morphologies. However, the elucidation of Aß molecules is essential because they are believed to play an important role in AD pathogenesis. Recent combination studies using nuclear magnetic resonance (NMR) and cryo-electron microscopy (cryo-EM) have primarily revealed more detailed information about their aggregation process, including fibril extension and secondary nucleation, and the structural polymorphism of the fibrils under a variety of some conditions, including the actual brain. This review attempts to summarize the existing information on the major properties of the structure and aggregation of Aß.