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

Article type: Research Article

Authors: Sundelöf, Johan^{a; *} | Sundström, Johan^b | Hansson, Oskar^c | Eriksdotter-Jönhagen, Maria^d | Giedraitis, Vilmantas^a | Larsson, Anders^b | Degerman-Gunnarsson, Malin^a | Ingelsson, Martin^a | Minthon, Lennart^c | Blennow, Kaj^{e; f} | Kilander, Lena^a | Basun, Hans^a | Lannfelt, Lars^a

Affiliations: [a] Uppsala University, Department of Public Health/Geriatrics, Uppsala, Sweden | [b] Uppsala University, Department of Medical Sciences, Uppsala, Sweden | [c] Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden; Neuropsychiatric Clinic, Malmö University Hospital, Sweden | [d] Department of Neuroscience, Caring Sciences and Society, Karolinska Institutet, Karolinska University, Hospital Huddinge, Stockholm, Sweden | [e] Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, Sahlgrenska University Hospital, Göteborg University, Sweden | [f] Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, Sweden

Correspondence: [*] Correspondence to: Johan Sundelöf, MD, Uppsala University, Dept. of Public Health/Geriatrics, Uppsala Science Park, Dag Hammarskölds väg 14B, 751 85 Uppsala, Sweden. Tel.: +46 18 611 79 63; Fax: +46 18 611 79 76; E-mail: johan.sundelof@pubcare.uu.se.

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.

Keywords: Alzheimer's disease, biomarkers, case control study, cystatin C, epidemiology, risk factor

DOI: 10.3233/JAD-2010-091594

Journal: Journal of Alzheimer's Disease, vol. 21, no. 2, pp. 471-478, 2010