Abstract
Small proteins like amyloid beta (Aβ) monomers are related to neurodegenerative disorders by aggregation to insoluble fibrils. Small angle neutron scattering (SANS) is a nondestructive method to observe the aggregation process in solution. We show that SANS is able to resolve monomers of small molecular weight like Aβ for aggregation studies. We examine Aβ monomers after prolonged storing in d-hexafluoroisopropanol (dHFIP) by using SANS and dynamic light scattering (DLS). We determined the radius of gyration from SANS as 1.0±0.1 nm for Aβ1–40 and 1.6±0.1 nm for Aβ1–42 in agreement with 3D NMR structures in similar solvents suggesting a solvent surface layer with 5% increased density. After initial dissolution in dHFIP Aβ aggregates sediment with a major component of pure monomers showing a hydrodynamic radius of 1.8±0.3 nm for Aβ1–40 and 3.2±0.4 nm for Aβ1–42 including a surface layer of dHFIP solvent molecules.
Highlights
A common pathologic hallmark of neurodegenerative disorders like Alzheimer’s, Parkinson’s or Huntington’s disease is the existence of amyloid deposits in the brain[1,2,3,4,5,6]
To examine the content of freshly in dHFIP dissolved Aβ powder we explored the evolution of the intensity correlation of Aβ1–40 and Aβ1–42 in dHFIP at 20°C by repeated dynamic light scattering (DLS) experiment
In this study we investigated the applicability of Small angle neutron scattering (SANS) to the study of the Alzheimer’s disease associated amyloid beta peptide (Aβ)
Summary
A common pathologic hallmark of neurodegenerative disorders like Alzheimer’s, Parkinson’s or Huntington’s disease is the existence of amyloid deposits in the brain[1,2,3,4,5,6]. Amyloid is generated by abnormal protein aggregation leading to formation of insoluble protein fibrils with a highly ordered cross-beta sheet structure. At the beginning of the 20th century beta amyloid protein (Aβ) was supposed to be associated with Alzheimer disease (AD) in consequence of the detection of Aβ fibril in intercellular plaques found in brain of AD patients[7]. Aβ is a hydrophobic protein with 39–43 amino acid residues, which is produced by proteolytic cleavage of amyloid precursor protein (APP) associated with the cell membrane[11]. The γ-secretase, within the membrane region, generates the fibrillogenic C-terminus of Aβ[12] and may cause an amount of isoforms dependent on the exact position for cleavage, where Aβ40 and Aβ42 are the most
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