Abstract
Aggregation states of amyloid beta peptides for amyloid beta A to A and Ap 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 Ap 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.
Highlights
The formation of neuritic plaques throughout the grey matter of the brain, associated with neurofibrillary tangles and neuronal loss, is responsible for neurodegenerative illnesses, such as the Alzheimer’s disease (AD) [1]
Representative SDS-PAGE has been used just to verify the presence of monomer, oligomer and fibrillary aggregates; the silver staining analysis is not intended as a definitive identification of all the various aggregation species prepared in vitro [15] and observed by small angle neutron scattering (SANS)
Aβ1–40, Aβ1–42 and Aβp3–42 peptides show a band at about 4 kDa; Aβ1–42 and Aβp3–42 monomeric preparations show the presence of spontaneous aggregates of low molecular weight (Figure 1)
Summary
The formation of neuritic plaques throughout the grey matter of the brain, associated with neurofibrillary tangles and neuronal loss, is responsible for neurodegenerative illnesses, such as the Alzheimer’s disease (AD) [1]. Electron microscopy studies have revealed that the plaques comprise a central mass of extracellular filaments called amyloid fibrils that radially extend toward the periphery, where they are tangled with dystrophic neurites as well as astrocytic and microglial processes [1]. The neurofibrillary tangles are fibril aggregates of the microtubule-associated protein tau, which has become hyperphosphorylated and accumulates inside the cells themselves [1]. Clinicopathological correlation studies have established that the neuritic plaque build-up occurs primarily in the brain before the onset of cognitive deficits, while neurofibrillary tangles and neuronal and synaptic loss are directly related to cognitive decline [1,2]. While the frequency and topographical extension of neuritic plaques increase with disease progression [4,5], their size inexplicably does not significantly grow over an average 50 μm in diameter [6,7]
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