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 β-amyloid protein (Aβ) 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 Aβ1-42 significantly attenuated the in vitro formation of Aβ 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 Aβ oligomers. Direct binding of cystatin C to Aβ 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 Aβ to larger and perhaps more toxic molecular species in vivo.
Original language | English |
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Pages (from-to) | 179-190 |
Number of pages | 12 |
Journal | Scandinavian Journal of Clinical and Laboratory Investigation |
Volume | 67 |
Issue number | 2 |
DOIs | |
State | Published - 2007 |
Bibliographical note
Funding Information:This study was supported by the Medicon Valley Research Council (Project no. 05196).
Keywords
- ADDLs
- Alzheimer's disease
- Beta amyloid protein
- Cysteine protease inhibitor
ASJC Scopus subject areas
- Clinical Biochemistry