Affiliations: [a] Proteomics Unit, IRCCS “Centro S. Giovanni di Dio-FBF”, Brescia, Italy | [b] NeuroBioGen Lab-Memory Clinic, IRCCS “Centro S. Giovanni di Dio-FBF”, Brescia, Italy | [c] Nathan S. Kline Institute, Orangeburg, NY, USA | [d] Departments of Pharmacology and Psychiatry, New York University School of Medicine New York, NY, USA | [e] Department of Health Sciences, Section of Psychiatry, University of Pavia, Pavia, Italy
Correspondence:
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Correspondence to: Roberta Ghidoni, Proteomics Unit, NeuroBioGen Lab-Memory Clinic, IRCCS “Centro San Giovanni di Dio-Fatebenefratelli”, via Pilastroni 4, 25125 Brescia, Italy. Tel.: +39 030 3501725; Fax: +39 030 3533513; E-mail: [email protected].
Abstract: 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.
