Aggregation and structure of amyloid β-protein

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 beta-protein (A beta) and neurofibrillary tangles of tau protein. Genetic studies, biochemical data, and animal models have suggested that A beta is a critical species in the pathogenesis of AD. A beta molecules aggregate to form oligomers, protofibrils (PFs), and mature fibrils. Because of their instability and structural heterogeneity, the misfolding and aggregation of A beta is a highly complex process, leading to a variety of aggregates with different structures and morphologies. However, the elucidation of A beta 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 A beta.

Automated summary

Alzheimer's disease is a common age-related neurodegenerative disorder characterized by plaques composed of amyloid beta-protein and neurofibrillary tangles of tau protein in the brain. Genetic studies have suggested that the misfolding and aggregation of Aβ molecules play a critical role in the pathogenesis of AD. Recent combination studies using NMR and cryo-EM have provided detailed information on the aggregation process and structural polymorphism of Aβ fibrils.