Cystatin C reduces the in vitro formation of soluble Aβ1-42 oligomers and protofibrils

M. L. Selenica, X. Wang, L. Ostergaard-Pedersen, A. Westlind-Danielsson, A. Grubb

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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 languageEnglish
Pages (from-to)179-190
Number of pages12
JournalScandinavian Journal of Clinical and Laboratory Investigation
Issue number2
StatePublished - 2007

Bibliographical note

Funding Information:
This study was supported by the Medicon Valley Research Council (Project no. 05196).


  • ADDLs
  • Alzheimer's disease
  • Beta amyloid protein
  • Cysteine protease inhibitor

ASJC Scopus subject areas

  • Clinical Biochemistry


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