Studies of the growth, evolution, and self‐aggregation of β‐amyloid fibrils using tapping‐mode atomic force microscopy

Abstract

Amyloid peptide (Aβ) is the major protein component of plaques found in Alzheimer's disease, and the aggregation of Aβ into oligomeric and fibrillic assemblies has been shown to be an early event of the disease pathway. Visualization of the progressive evolution of nanoscale changes in the morphology of Aβ oligomeric assemblies and amyloid fibrils has been accomplished ex situ using atomic force microscopy (AFM) in ambient conditions. In this report, the size and the shape of amyloid β(1-40) fibrils, as well as the secondary organization into aggregate structures were monitored at different intervals over a period of 5 months. Characterizations with tapping-mode AFM serve to minimize the strong adhesive forces between the probe and the sample to prevent damage or displacement of fragile fibrils. The early stages of Aβ growth showed a predominance of spherical seed structures, oligomeric assemblies, and protofibrils; however the size and density of fibrils progressively increased with time. Within a few days of incubation, linear assemblies and fibrils became apparent. Over extended time scales of up to 5 months, the fibrils formed dense ensembles spanning lengths of several microns, which exhibit interesting changes due to self-organization of the fibrils into bundles or tangles. Detailed characterization of the Aβ assembly process at the nanoscale will help elucidate the role of Aβ in the pathology of Alzheimer's disease.

Alzheimer’s Disease Amyloid Peptides Interact with DNA, As Proved by Surface Plasmon Resonance

“…This dimension is in very good agreement with that described by Serem et al for the small spherical oligomers which they can observe by AFM [45]. As described by the same authors, a fibrillar aggregation starts with the aging of the peptide solution to yield, after several weeks, a high peptide fibrillation.…”

Biophysical Insights into How Surfaces, Including Lipid Membranes, Modulate Protein Aggregation Related to Neurodegeneration

“…The ability to circumvent the lag-phase of amyloid formation by adding preformed aggregates in a process called seeding (Jarrett and Lansbury, 1993; Lansbury, 1997; Paravastu et al, 2006; Nonaka et al, 2010; Jucker and Walker, 2011; Serem et al, 2011), demonstrating that such seeds can impose aberrant structure on other proteins. Such a phenomenon appears to play a role in the cell to cell translation of the disease state across specific regions of the brain (Vonsattel and DiFiglia, 1998; Braak et al, 2003; Ravits et al, 2007; Braak and Del Tredici, 2011), and this is reminiscent of the infectious nature of prions.…”

Amyloid β-Protein Assembly and Alzheimer’s Disease: Dodecamers of Aβ42, but Not of Aβ40, Seed Fibril Formation

“…11–13 It has been suggested in AFM studies that small Aβ oligomers act as seeds that induce oligomerization of adjacent monomers, similar to the mechanism of template-mediated prion conversion. 6,14,15 Studies using ion-mobility based mass spectrometry (IMS-MS) have attempted to address exactly which types of oligomers are formed and whether these oligomers act as seeds for fibril growth. 16,17 These studies revealed that even order oligomers were dominant, 2, 4, 6 and 12 with high populations of hexamers and dodecomers.…”