Cystatin C Levels are Positively Correlated with both Aβ42 and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (A beta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, A beta(42), 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, A beta(42), and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, A beta(42), and tau levels across disease groups were investigated. Cystatin C, A beta(42), total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (A beta 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 mu mol/L +/- 1.7), MCI (5.4 mu mol/L +/- 1.48), and controls (5.6 mu mol/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 A beta(42) (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 A beta(42) levels in CSF independent of age, gender, and APOE genotype.