Solid-State Structure of Abeta (Aβ) in Alzheimer's Disease

Alzheimer's disease (AD) has become the most common neurodegenerative disease. The deposition of amyloid fibrils in the brain is one of the characteristics of AD. The fibrils are composed of amyloid-beta peptide (A beta). A beta is produced through a series event of protease cleavage of a transmembrane protein called beta-amyloid precursor protein (APP) which is commonly expressed in the brain. The production of A beta and its propensity to aggregation to form oligomers and fibrils are believed to initiate a sequence of events that lead to AD dementia. The production of A beta is influenced by the transmembrane domain (TM) structure of APP. The structure variety of different A beta assemblies including oligomers and fibrils may result in different neurotoxicity to the brain. Therefore, enormous work has been carried out to study the structure of APP TM and various A beta assemblies. Solid-state NMR has advantages in studying immobile protein structures with large molecular weight. In this review, solid-state NMR structure of APP TM and different A beta assemblies will be discussed, especially various A beta amyloid fibril structures. This structural information greatly enhanced our understanding in AD, providing fundamental knowledge that will help in finding a treatment for AD.