In vitro amyloid Aβ1-42 peptide aggregation monitoring by asymmetrical flow field-flow fractionation with multi-angle light scattering detection

Rambaldi, Diana C.; Zattoni, Andrea; Reschiglian, Pierluigi; Colombo, Raffaella; De Lorenzi, Ersilia
August 2009
Analytical & Bioanalytical Chemistry;Aug2009, Vol. 394 Issue 8, p2145
Academic Journal
Self-assembly of the 42-amino-acid-long amyloid peptide Aβ1-42 into insoluble fibrillar deposits in the brain is a crucial event in the pathogenesis of Alzheimer's disease. The fibril deposition occurs through an aggregation process during which transient and metastable oligomeric intermediates are intrinsically difficult to be accurately monitored and characterised. In this work, the time-dependent Aβ1-42 aggregation pattern is studied by asymmetrical flow field-flow fractionation with on-line multi-angle light scattering detection. This technique allows separating and obtaining information on the molar mass ( Mr) and size distribution of both the early-forming soluble aggregates and the late prefibrillar and fibrillar species, the latter having very high Mr. Preliminary results demonstrate that unique information on the dynamic aggregation process can be obtained, namely on the Mr and size of the forming aggregates as well as on their formation kinetics.


Related Articles

  • Prediction of "hot spots" of aggregation in disease-linked polypeptides. de Groot, Natalia Sánchez; Pallarés, Irantzu; Avilés, Francesc X.; Vendrell, Josep; Salvador Ventura // BMC Structural Biology;2005, Vol. 5, p18 

    Background: The polypeptides involved in amyloidogenesis may be globular proteins with a defined 3D-structure or natively unfolded proteins. The first class includes polypeptides such as β2- microglobulin, lysozyme, transthyretin or the prion protein, whereas β-amyloid peptide, amylin or...

  • A new methodology for simultaneous quantification of total-Aβ, Aβx-38, Aβx-40, and Aβx-42 by column-switching LC/MS/MS. Watanabe, Ken-ichi; Ishikawa, Chihiro; Kuwahara, Hiroshi; Sato, Kimihiko; Komuro, Setsuko; Nakagawa, Tetsuya; Nomura, Naruaki; Watanabe, Shiro; Yabuki, Masashi // Analytical & Bioanalytical Chemistry;Apr2012, Vol. 402 Issue 6, p2033 

    This article details the development of a novel method that overcomes the drawbacks of sandwich ELISA (sELISA) and allows reliable evaluation of simultaneous quantification of the amyloid (Aβ)-peptides, total-Aβ, Aβx-38, Aβx-40, and Aβx-42, in rat brain by optimized sample...

  • Atomic Force Microscopy Study of Human Amylin (20-29) Fibrils. Sedman, Victoria L.; Allen, Stephanie; Chan, Weng C.; Davies, Martyn C.; Roberts, Clive J.; Tendler, Saul J. B.; Williams, Philip M. // Protein & Peptide Letters;Jan2005, Vol. 12 Issue 1, p79 

    Here we present atomic force microscopy images of the fibrils formed by human amylin(20-29). This peptide is a fragment of the polypeptide amylin, the major proteinaceous component of amyloid deposits found in cases of type-II diabetes mellitus. Our results demonstrate that the amylin(20-29)...

  • Lessons from two prevalent amyloidoses—what amylin and Aβ have in common. Götz, Jürgen; Lim, Yun-An; Eckert, Anne // Frontiers in Aging Neuroscience;Aug2013, Vol. 5, p1 

    The amyloidogenic peptide Aβ plays a key role in Alzheimer's disease (AD) forming insoluble aggregates in the brain. The peptide shares its amyloidogenic properties with amylin that forms aggregates in the pancreas of patients with Type 2 Diabetes mellitus (T2DM). While epidemiological...

  • Soluble aggregates of the amyloid-p peptide are trapped by serum albumin to enhance amyloid-β activation of endothelial cells. Barcelo, Adriana A. Reyes; Gonzalez-Velasquez, Francisco J.; Moss, Melissa A. // Journal of Biological Engineering;2009, Vol. 3, p1 

    Background: Self-assembly of the amyloid-β peptide (Aβ) has been implicated in the pathogenesis of Alzheimer's disease (AD). As a result, synthetic molecules capable of inhibiting Aβ self-assembly could serve as therapeutic agents and endogenous molecules that modulate Aβ...

  • How Cholesterol Constrains Glycolipid Conformation for Optimal Recognition of Alzheimer's β Amyloid Peptide (Aβ1-40). Yahi, Nouara; Aulas, Anaïs; Fantini, Jacques // PLoS ONE;2010, Vol. 5 Issue 2, p1 

    Membrane lipids play a pivotal role in the pathogenesis of Alzheimer's disease, which is associated with conformational changes, oligomerization and/or aggregation of Alzheimer's β-amyloid (Aβ) peptides. Yet conflicting data have been reported on the respective effect of cholesterol and...

  • Quasielastic Light Scattering Study of Amyloid �-Protein Fibril Formation. Lomakin, Aleksey; Teplow, David B. // Protein & Peptide Letters;Mar2006, Vol. 13 Issue 3, p247 

    Quasielastic light scattering spectroscopy (QLS) is an optical method for the determination of diffusion coefficients of particles in solution. Here we discuss the principles of QLS and explain how the distribution of particle sizes can be reconstructed from the measured correlation function of...

  • GEPT Extract Reduces Aβ Deposition by Regulating the Balance Between Production and Degradation of Aβ in APPV717I Transgenic Mice. Jinzhou Tian; Jing Shi; Leiming Zhang; Junxiang Yin; Quan Hu; Yi Xu; Shuli Sheng; Pengwen Wang; Ying Ren; Rong Wang; Yongyan Wang // Current Alzheimer Research;Apr2009, Vol. 6 Issue 2, p118 

    Background: Accumulation of beta-amyloid peptide (Aβ) in the brain is a primary influence driving Alzheimer's disease (AD) pathogenesis. The disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between production and...

  • Amyloidogenic properties of the artificial protein albebetin and its biologically active derivatives. The role of electrostatic interactions in fibril formation. Lavrikova, M. A.; Zamotin, V. V.; Malisauskas, M.; Chertkova, R. V.; Kostanyan, I. A.; Dolgikh, D. A.; Kirpichnikov, M. P.; Morozova-Roche, L. A. // Biochemistry (00062979);Mar2006, Vol. 71 Issue 3, p306 

    The artificial protein albebetin (ABB) and its derivatives containing biologically active fragments of natural proteins form fibrils at physiological pH. The amyloid nature of the fibrils was confirmed by far UV circular dichroism spectra indicating for rich β-structure, thioflavin T binding...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics