Cystatin C (encoded by the CST3 gene) is a member of the type 2 cystatin family of cysteine protease inhibitors[1]. It is a secreted protein found in most body fluids, with particularly high concentrations in cerebrospinal fluid (CSF). Cystatin C plays important roles in normal physiology and has been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease and cerebral amyloid angiopathy[2].
Cystatin C is a 120-amino acid, non-glycosylated protein with a molecular weight of approximately 13.3 kDa. Key structural features include:
The protein adopts a wedge-shaped structure that allows it to bind to and inhibit cysteine proteases of the papain family[3].
Cystatin C's primary function is to inhibit cysteine proteases:
The CST3 gene has been associated with Alzheimer's disease risk:
Cystatin C is evaluated as a potential biomarker:
Cystatin C interacts with amyloid-beta (Aβ) in several ways[4]:
Cystatin C is a major component of amyloid deposits in cerebral amyloid angiopathy (CAA):
Abrahamson M, et al. Structure and function of cystatin C. Biol Chem Hoppe Seyler. 1994. ↩︎
Mathews PM, Levy E. Cystatin C in aging and in Alzheimer's disease. Lancet Neurol. 2016. ↩︎
Turk V, et al. Cystatins: from evolution to clinical applications. FEBS J. 2020. ↩︎
Berkenstad K, et al. Cystatin C and amyloid-beta interactions in Alzheimer's disease. Acta Neuropathol Commun. 2019. ↩︎
Gkanatsiou E, et al. Cerebral amyloid angiopathy and cystatin C. Brain. 2018. ↩︎