Plasma cystatin c and risk of developing Alzheimer's disease in subjects with mild cognitive impairment

Roberta Ghidoni, Luisa Benussi, Michela Glionna, Silvia Desenzani, Valentina Albertini, Efrat Levy, Enzo Emanuele, Giuliano Binetti

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Recent years have witnessed an increasing interest in mild cognitive impairment (MCI), particularly as a possible prodromal stage of Alzheimer's disease (AD). Experimental and clinical data have suggested that cystatin C (CysC) is protective against the development of AD. In this study, we sought to cross-sectionally and longitudinally investigate the changes in plasma CysC levels in patients with MCI and whether the levels of this molecule might serve as a biochemical predictor of cognitive decline in this patient group. Cross-sectional analysis of baseline data showed a borderline significant difference in plasma CysC levels among the three study groups (Controls, n=63; AD, n=63; MCI, n=59) (p =0.032) that disappeared after post hoc analysis. Plasma CysC levels did not differ at baseline (t1) and at follow-up (t2) both in MCI patients that converted to AD (n= 32) and those that did not convert (n=27). However, a significant independent association between CysC at t1 and CysC at t2 was found in non-converters but not in converters MCI subjects. Moreover, when disease onset was evaluated in patients groups stratified on the basis of their CysC plasma levels, a significant anticipation of the conversion to dementia in MCI subjects with CysC levels below the median (CysC <1067 ng/ml) (p =0.0011) was observed. Altogether, this work adds to the growing body of literature suggesting that CysC modulates the clinical expression of cognitive decline, and opens a new area of investigation of CysC as a therapeutic target for neurodegenerative disorders.

Original languageEnglish
Pages (from-to)985-991
Number of pages7
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - 2010


  • Amyloid
  • APOE
  • biomarkers
  • cystatins
  • dementia
  • humans
  • longitudinal studies
  • plasma

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology


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