Cystatin C role in Alzheimer disease: From neurodegeneration to neuroregeneration

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

In the brain cystatin C is synthesized by the choroid plexus and leptomeningeal cells, and it is localized in glial cells and in neurons. Its physiological high concentration in the cerebrospinal fluid (CSF) of the central nervous system and its proliferative effect on neural rat stem cells strongly suggest that cystatin C could exert a trophic function in the brain. Acute and chronic neurodegenerative processes induce an increase of cystatin C expression levels, mainly in activated glial cells. In brains from Alzheimer disease (AD) patients neuronal concentration of cystatin C protein is increased and its association to beta-amyloid peptide (A-beta) was revealed. A direct interaction of cystatin C and A-beta, resulting in an inhibition of amyloid formation, was demonstrated. An involvement of cystatin C in the pathogenesis of AD was further suggested by genetic studies in which the allelic haplotype B in cystatin C gene (CST3), determining an Ala25Thr substitution in the signal peptide, was associated with risk to develop late-onset AD. The B/B haplotype is specifically associated to highly reduced levels of extracellular cystatin C. In this view, the molecular correlate of the genetic risk conferred by cystatin C B variant could be the reduction in cystatin C secretion, which may result in A-beta formation and deposition. Alternatively, a reduced secretion of this protein could cause an impairment in neuroregeneration in response to brain damage.

Original languageEnglish
Title of host publicationAlzheimer's Disease Diagnosis and Treatments
PublisherNova Science Publishers, Inc.
Pages231-241
Number of pages11
ISBN (Print)9781611220643
Publication statusPublished - Jan 2011

Keywords

  • Alzheimer disease
  • Amyloid-β peptide
  • Amyloidosis
  • CST3
  • Cystatin C

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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