Cystatin C Levels are Positively Correlated with both Aβ 42 and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease,Mild Cognitive Impairment,and Healthy Controls

Abstract

Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-β (Aβ) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, Aβ₄₂, and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, Aβ₄₂, and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, Aβ₄₂, and tau levels across disease groups were investigated. Cystatin C, Aβ₄₂, total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (Aβ and tau) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Mean cystatin C levels were similar in cases of AD (5.6 μmol/L ± 1.7), MCI (5.4 μmol/L ± 1.48), and controls (5.6 μmol/L ± 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r=0.61–0.81, p< 0.0001) and Aβ₄₂ (r=0.35–0.65, p< 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and Aβ₄₂ levels in CSF independent of age, gender, and APOE genotype.