Structural Biochemistry/β-amyloid

β-amyloid (Aβ peptide)
It is a peptide which is a proteolytic fragment of amyloid precursor protein. The peptide possesses an amphiphilic structure, which has both hydrophilic N-terminus and hydrophobic C-terminus. The two distinct form of the peptide are Aβ(1–40), which consists of 40 residues and Aβ(1–42), which consists of 42 residues. The modification of this peptide is sometimes the cause of Alzheimer’s disease.

Aβ amyloid fibrils
Fibrillar poly peptide aggregates with a cross- β structure. The cross- β structure of the amyloid fibrils shows the polypeptide assemblies; β-sheet plane and the backbone hydrogen bonds are oriented parallel to the main fibril axis. There are zipper units which consist of a pair of two cross- β sheets with interdigitation side chains and the zipper units constitute the structural spine of amyloid fibrils. The amyloid fibrils display the typical characteristics depending on the Aβ peptide. For example, β-sheet variability of the fibrils comes from Aβ and its derived peptide fragments or variants. The structural polymorphism of amyloid fibrils is the diversity of intrafibrillar composition or peptide conformation of different fibrils. The three forms of polymorphism that can occur between different fibrils are the amount, relative orientation, and substructures of the comprising protofilaments. Polymorphism is a significant feature of amyloid fibrils because it is responsible for the biophysical variation between natural protein folding reactions and amyloid fibril arrangement. Additionally, it possibly causes the variability of certain amyloid pathologies.

Cause of Alzheimer’s Disease(AD)


Aβ, which is the main component of the amyloid plaques (deposits found in the brains of patients with Alzheimer’s disease), and neurofibrillary tangles (deposits found in the brains of patients with Alzheimer’s disease) contribute to the degradation of the neurons in the brain, and consequently causes the Alzheimer disease. When amyloid plaques are deformed in the process of bending or twisting, the AD can be onset.

Amyloid Plaques

Amyloid is a protein fragments that body produces normally and when this amyloid plaques are accumulated between nerve cells in the brain, Alzheimer disease is on set.

Neurofibrillary Tangles

They are insoluble twisted fibers and found inside the brain’s cells. There is a protein called tau, and the protein which helps the transportation of nutrients, does not function normally in Alzheimer's disease.

Structural methods for studying amyloid fibrils
There are two potential methods to determine the structure of Aβ amyloid fibrils at atomic or near-atomic resolutions

1.	NMR technique

It determines the structural constraints such as chemical shift values, bond angles, or specific interatomic distances. Through NMR technique, the residues of Aβ participating in the β-sheet structure in fibrils are identified.

2.	Cryomicroscopy (cryo-EM)

It visualizes the fibrils and allows the calculation of their 3D density. The visualized fibrils make selection of specific fibril morphologies possible and therefore, only data from a chosen morphology will be averaged in 3D reconstruction. This technique provides the information about the global fibril architecture, protofilament substructure, and location of the cross-β structure within the symmetric fibril helix.