Higher Cathepsin B Levels in Plasma in Alzheimer's Disease Compared to Healthy Controls

Article type: Research Article

Authors: Sundelöf, Johan^{a; *} | Sundström, Johan^b | Hansson, Oskar^{c; d} | Eriksdotter-Jönhagen, Maria^e | Giedraitis, Vilmantas^a | Larsson, Anders^b | Degerman-Gunnarsson, Malin^a | Ingelsson, Martin^a | Minthon, Lennart^{c; d} | Blennow, Kaj^{f; g} | 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, Lund, Sweden | [d] Neuropsychiatric Clinic, Skåne University Hospital, Malmö, Sweden | [e] Department of Neuroscience, Caring Sciences and Society, Karolinska Institutet, Karolinska University, Hospital Huddinge, Stockholm, Sweden | [f] Institute of Neurobiology and Physiology, Department of Neurochemistry and Psychiatry, Sahlgrenska University Hospital, Göteborg University, Sweden | [g] 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.: +4618 611 79 63; Fax +4618 611 79 76, E-mail: johan.sundelof@pubcare.uu.se.

Abstract: Cathepsin B is suggested to be involved in amyloid-β (Aβ) processing and Alzheimer's disease (AD). Studies of cathepsin B levels in plasma and cerebrospinal fluid (CSF) have not been previously performed. We examined cathepsin B levels in plasma and CSF samples in persons with AD, mild cognitive impairment (MCI), and healthy controls in order to test the hypothesis that cathepsin B levels can discriminate persons with AD or MCI from healthy controls. Cathepsin B, Cystatin C, Aβ1–40 and Aβ1–42, total tau, phosphorylated tau, and albumin levels in plasma and CSF were analyzed by ELISA (Cathepsin B) turbidimetry (cystatin C), xMAP Luminex technology (Aβ1–40 and Aβ1–42 and tau), and Cobas C501 analyzer (albumin) in persons with AD (n = 101), MCI (n = 84), and healthy control subjects (n = 28). Plasma cathepsin B levels were higher in persons with AD compared to healthy controls, both in unadjusted models and in multivariable models adjusting for age, gender, APOE genotype, cystatin C, and albumin levels: Odds ratio (OR) for AD per 1 SD of plasma cathepsin B; 2.04, 95% confidence interval (CI); 1.01–4.14, p = 0.05. There was no difference between diagnostic groups in cathepsin B levels in CSF: OR for AD per 1 SD of CSF cathepsin B; 0.93, 95% CI; 0.37–2.30, p = 0.87. Plasma cathepsin B levels were higher in persons with AD compared to healthy controls whereas there was no difference between diagnostic groups in cathepsin B levels in CSF. Further investigation of cathepsin B as a predictor of AD is warranted.

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

DOI: 10.3233/JAD-2010-101023

Journal: Journal of Alzheimer's Disease, vol. 22, no. 4, pp. 1223-1230, 2010