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

Research output: Contribution to journalArticle

Standard

Cystatin C reduces the in vitro formation of soluble A beta 1-42 oligomers and protofibrils. / Selenica, M. L.; Wang, Xin; Ostergaard-Pedersen, L.; Westlind-Danielsson, A.; Grubb, Anders.

In: Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 67, No. 2, 2007, p. 179-190.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Selenica, M. L. ; Wang, Xin ; Ostergaard-Pedersen, L. ; Westlind-Danielsson, A. ; Grubb, Anders. / Cystatin C reduces the in vitro formation of soluble A beta 1-42 oligomers and protofibrils. In: Scandinavian Journal of Clinical & Laboratory Investigation. 2007 ; Vol. 67, No. 2. pp. 179-190.

RIS

TY - JOUR

T1 - Cystatin C reduces the in vitro formation of soluble A beta 1-42 oligomers and protofibrils

AU - Selenica, M. L.

AU - Wang, Xin

AU - Ostergaard-Pedersen, L.

AU - Westlind-Danielsson, A.

AU - Grubb, Anders

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - cysteine protease

KW - beta amyloid protein

KW - ADDLs

KW - Alzheimer's disease

KW - inhibitor

U2 - 10.1080/00365510601009738

DO - 10.1080/00365510601009738

M3 - Article

VL - 67

SP - 179

EP - 190

JO - Scandinavian Journal of Clinical & Laboratory Investigation

JF - Scandinavian Journal of Clinical & Laboratory Investigation

SN - 1502-7686

IS - 2

ER -