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    Simultaneous measurement of a range of particle sizes during Ab1–42 fibrillogenesis quantified using fluorescence correlation spectroscopy


    Mittag, Judith J. and Milani, Silvia and Walsh, Dominic M. and Rädler, Joachim O. and McManus, Jennifer J. (2015) Simultaneous measurement of a range of particle sizes during Ab1–42 fibrillogenesis quantified using fluorescence correlation spectroscopy. Biochemical and Biophysical Research Communications, 448 (2). pp. 195-199. ISSN 0006-291X

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    Abstract

    Low molecular weight oligomers of amyloid beta (Aβ) are important drivers of Alzheimer's disease. A decrease in Aβ monomer levels in human cerebrospinal fluid (CSF) is observed in Alzheimers' patients and is a robust biomarker of the disease. It has been suggested that the decrease in monomer levels in CSF is due to the formation of Aβ oligomers. A robust technique capable of identifying Aβ oligomers in CSF is therefore desirable. We have used fluorescence correlation spectroscopy and a five Gaussian distribution model (5GDM) to monitor the aggregation of Aβ1-42 in sodium phosphate buffer and in artificial cerebrospinal fluid (ACSF). In buffer, several different sized components (monomer, oligomers, protofibrils and fibrils) can be identified simultaneously using 5GDM. In ACSF, the faster kinetics of fibrillogenesis leads to the formation of fibrils on very short timescales. This analysis method can also be used to monitor the aggregation of other proteins, nanoparticles or colloids, even in complex biological fluids.

    Item Type: Article
    Keywords: Aggregation; Alzheimer’s disease; Amyloid beta; Fluorescence correlation spectroscopy; Oligomerization; Protein folding disease;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 7754
    Identification Number: https://doi.org/10.1016/j.bbrc.2014.04.088
    Depositing User: Jennifer McManus
    Date Deposited: 13 Jan 2017 17:02
    Journal or Publication Title: Biochemical and Biophysical Research Communications
    Publisher: Elsevier
    Refereed: Yes
    Funders: Science Foundation Ireland (SFI), European Science Foundation, Deutsche Forschungsgemeinschaft, Foundation for Neurologic Diseases
    URI:

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