Long-Term Stability of Alzheimer's Disease Biomarker Proteins in Cerebrospinal Fluid

Article type: Research Article

Authors: Schipke, Carola G.^a | Jessen, Frank^{b; i} | Teipel, Stefan^{c; j} | Luckhaus, Christian^d | Wiltfang, Jens^e | Esselmann, Hermann^e | Frölich, Lutz^f | Maier, Wolfgang^{b; i} | Rüther, Eckart^g | Heppner, Frank L.^h | Prokop, Stefan^h | Heuser, Isabella^a | Peters, Oliver^{a; *}

Affiliations: [a] Department of Psychiatry, Charité, CBF, Berlin, Germany | [b] Department of Psychiatry, University Bonn, Bonn, Germany | [c] Department of Psychiatry, University Rostock, Rostock, Germany | [d] Department of Psychiatry, Heinrich-Heine University, Düsseldorf, Germany | [e] Department of Psychiatry, University Essen, Essen, Germany | [f] Central Institute of Mental Health, Mannheim, Germany | [g] Department of Psychiatry, University Göttingen, Göttingen, Germany | [h] Department of Neuropathology, Charité, CCM, Berlin, Germany | [i] DZNE, German Center for Neurodgenerative Disorder, Bonn, Germany | [j] DZNE, German Center for Neurodgenerative Disorder, Rostock, Germany

Correspondence: [*] Correspondence to: Dr. Oliver Peters, Department of Psychiatry and Psychotherapy, Charité – Universiätsmedizin Berlin, CBF, Eschenallee 3, 14050 Berlin, Germany. Tel.: +49 30 8445 8215; Fax: +49 30 8445 8255; E-mail: [email protected].

Abstract: The quantitative analysis of peptides in human cerebrospinal fluid (CSF) has become an important step in the early diagnosis of dementia, e.g., Alzheimer's disease. In search of new biomarkers for early detection and differential diagnosis of chronic neurodegenerative diseases, “biobanking” and long-term storage of human samples is increasingly important. The German Dementia Competence Network (DCN) has accomplished one of the largest biomaterial banks in this field, comprising CSF from several hundreds of patients. Since little is known about long-term stability of biomarker proteins in frozen CSF, we investigated the reliability of quantitative analysis in a total of 56 CSF samples that had been frozen for up to six years. Here, we compare a second quantitative analysis of Aβ40, Aβ42, and the total-tau protein after several years of storage at −80°C with initial results obtained within six months after lumbar puncture. The second analysis was done using standard ELISAs or the newly developed Mesocale System. We found that regarding Aβ42 and total-tau, the results highly correlate with correlation coefficients of c = 0.73 and c = 0.82 respectively, while for Aβ40 the correlation coefficient was lower (c = 0.53), suggesting that Aβ40 is more vulnerable to degradation. We conclude that the quantitative analysis of the concentration of Aβ42, as well as for total-tau, in CSF in samples that have been stored for years is reliable. The determination of these biomarkers and potentially new biomarkers in CSF samples stored in large biomaterial banks assembled over many years is feasible.

Keywords: Alzheimer's disease, amyloid-β protein, biomarkers, cerebrospinal fluid, protein stability, tau-protein

DOI: 10.3233/JAD-2011-110329

Journal: Journal of Alzheimer's Disease, vol. 26, no. 2, pp. 255-262, 2011