Aggregation States of Aβ1–40, Aβ1–42 and Aβp3–42 Amyloid Beta Peptides: A SANS Study

Abstract

Aggregation states of amyloid beta peptides for amyloid beta A β 1 – 40 to A β 1 – 42 and A β p 3 – 42 are investigated through small angle neutron scattering (SANS). The knowledge of these small peptides and their aggregation state are of key importance for the comprehension of neurodegenerative diseases (e.g., Alzheimer’s disease). The SANS technique allows to study the size and fractal nature of the monomers, oligomers and fibrils of the three different peptides. Results show that all the investigated peptides have monomers with a radius of gyration of the order of 10 Å, while the oligomers and fibrils display differences in size and aggregation ability, with A β p 3 – 42 showing larger oligomers. These properties are strictly related to the toxicity of the corresponding amyloid peptide and indeed to the development of the associated disease.

Oligomerization and Conformational Change Turn Monomeric β-Amyloid and Tau Proteins Toxic: Their Role in Alzheimer’s Pathogenesis

“…The determination of fAβ structure has been a challenge owing to its structural polymorphism. Several physicochemical, spectroscopic, and biochemical techniques (solid-state NMR, high-speed atomic force microscopy [66], transition microscopy, Raman and 2D infrared spectroscopy [67], X-ray fiber diffraction, small angle neutron scattering [68,69], cryo-EM) [70] have been used for structural analysis of AβOs and fibrils. Computational studies have also been used for studying conformational dynamics and stability of different Aβ assemblies [71,72].…”

Interaction of Aβ42 with Membranes Triggers the Self-Assembly into Oligomers

“…Growing evidence suggests the involvement of protein oligomers in the development of protein misfolding diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD); however, limited knowledge exists regarding the molecular mechanisms behind the aggregation processes for these oligomers [1][2][3][4]. The amyloid cascade hypothesis (ACH), proposed more than a quarter-century ago [5], is the major model used to describe the pathology of AD and other neurodegenerative diseases [5][6][7][8][9].…”

On the Cluster Formation of α-Synuclein Fibrils

“…In Figure 3 , the simulated scattering curve is also compared with the analytical Beaucage model ( Hammouda 2010 ). Beaucage model describes fractal objects, and it has been used to describe amyloid fractals formed by amyloid-β, a protein involved in Alzheimer’s disease ( Festa et al, 2019a ; Festa et al, 2019b ). The model describes a low q Guinier regime, followed by a Porod regime with a power law -dependence of the intensity, q -d , for , again being the radius of gyration.…”