The soluble transcobalamin receptor (sCD320) is present in cerebrospinal fluid and correlates to dementia-related biomarkers tau proteins and amyloid-beta

Abstract

Background. Cellular uptake of vitamin B12 (B12) demands binding of the vitamin to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320. Recently, we identified a soluble form of CD320 (sCD320) in human plasma. Here we present data on the occurrence of this soluble receptor in cerebrospinal fluid (CSF) and show its correlations to dementia-related biomarkers tau proteins and amyloid-beta. Methods. We collected 223 cerebrospinal fluid samples and corresponding plasma samples (n = 46). We measured CSF and plasma sCD320, holoTC and total TC employing in-house ELISA methods and CSF phospho-tau (181P) (p-tau), total tau (t-tau) and amyloid-beta 1-42 (Aβ) (n = 177) employing commercial ELISA kits (Innogenetics Company). Size exclusion chromatography was performed on a Superdex 200 column. Results. The median sCD320 concentration in CSF (14 pmol/L) is around five times lower than in plasma (72 pmol/L). No correlation was observed between plasma and CSF sCD320 levels (n = 46), while the behavior upon size exclusion chromatography was the same. In CSF, sCD320 correlates to holoTC and total TC (Spearman’s correlation (R_s) = 0.325, 0.232 (n = 218, 217) respectively, p < 0.01). Interestingly, sCD320 correlates to p-tau and t-tau (R_s = 0.599, 0.569 (n = 173, 176) respectively, p < 0.001) and to Aβ (R_s = 0.265, p < 0.001 (n = 177)). Conclusion. We document for the first time the occurrence of sCD320 in human CSF. We report that the concentration of sCD320 correlates to the dementia-related biomarkers p-tau, t-tau and Aβ.

Key Words::

• CD320
• cobalamin
• vitamin B12
• phosphorylated tau
• amyloid beta-protein (1-42)

Acknowledgements

We warmly appreciate the excellent technical assistance offered by Inger Marie Jensen and Jette Fisker.

Declaration of interest:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by Aarhus University Research Foundation [AUFF-F2012-FLS 3-37] and the Lundbeck Foundation.