Simultaneous measurement of a range of particle sizes during Aβ1-42 fibrillogenesis quantified using fluorescence correlation spectroscopy.
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.
Ludwig-Maximilians-Universität, Fakultät für Physik & CeNS, Geschwister-Scholl-Platz 1, 80539 München, Germany. Electronic address: judith.mittag@physik.lmu.de.
Judith J
JJ
Mittag
Ludwig-Maximilians-Universität, Fakultät für Physik & CeNS, Geschwister-Scholl-Platz 1, 80539 München, Germany. Electronic address: silvia.milani@physik.lmu.de.
Silvia
S
Milani
Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Institutes of Medicine, Boston, MA 02115, USA. Electronic address: dwalsh3@partners.org.
Dominic M
DM
Walsh
Ludwig-Maximilians-Universität, Fakultät für Physik & CeNS, Geschwister-Scholl-Platz 1, 80539 München, Germany. Electronic address: raedler@lmu.de.
Joachim O
JO
Rädler
Department of Chemistry, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland. Electronic address: Jennifer.mcmanus@nuim.ie.
Jennifer J
JJ
McManus
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000134:cerebrospinal fluid / Q000737:chemistry* / Q000378:metabolism; D002021:Buffers; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008962:Models, Theoretical; D016011:Normal Distribution; D010316:Particle Size; D010446:Peptide Fragments / Q000032:analysis* / Q000134:cerebrospinal fluid / Q000737:chemistry* / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods*
D016229:Amyloid beta-Peptides; D002021:Buffers; D010446:Peptide Fragments; D010710:Phosphates; C075222:amyloid beta-protein (1-42); C018279:sodium phosphate
Aggregation; Alzheimer’s disease; Amyloid beta; Fluorescence correlation spectroscopy; Oligomerization; Protein folding disease