Cystatin C reduces the in vitro formation of soluble A beta 1-42 oligomers and protofibrils

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Bibtex

@article{8386e901ae224e7ab2ecded7e80e5f7f,
title = "Cystatin C reduces the in vitro formation of soluble A beta 1-42 oligomers and protofibrils",
abstract = "There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (A beta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co-incubation of cystatin C with monomeric A beta 1-42 significantly attenuated the in vitro formation of A beta oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, thioflavin T (ThT) spectrofluorimetry and gel chromatography. However, cystatin C did not dissolve preformed A beta oligomers. Direct binding of cystatin C to A beta was demonstrated with the formation of an initial 1:1 molar high-affinity complex. These observations suggest that cystatin C might be a regulating element in the transformation of monomeric A beta to larger and perhaps more toxic molecular species in vivo.",
keywords = "cysteine protease, beta amyloid protein, ADDLs, Alzheimer's disease, inhibitor",
author = "Selenica, {M. L.} and Xin Wang and L. Ostergaard-Pedersen and A. Westlind-Danielsson and Anders Grubb",
year = "2007",
doi = "10.1080/00365510601009738",
language = "English",
volume = "67",
pages = "179--190",
journal = "Scandinavian Journal of Clinical & Laboratory Investigation",
issn = "1502-7686",
publisher = "Informa Healthcare",
number = "2",

}