Impact of Preanalytical Procedures on Complement Biomarkers in Cerebrospinal Fluid and Plasma from Controls and Alzheimer's Disease Patients.

Background

Studies comparing cerebrospinal fluid (CSF) and plasma complement proteins in Alzheimer's disease (AD) patients versus healthy controls (HC) have yielded inconsistent results. Discrepancies in the preanalytical sample handling could contribute to the heterogeneity in the reported findings.

Objective

Using qualified immunoassays, we aimed at assessing the impact of preanalytical procedures on complement proteins in blood and CSF from AD patients and HCs.

Methods

We supplemented HC and AD CSF/plasma with complement stabilizers and measured the complement proteins C4a, C4, C3a, C3, Factor Bb and Factor B by immunoassay. We tested the impact of freeze-thaw (FT) cycles on fluid complement proteins.

Results

Most complement proteins were mildly impacted by FT cycles in plasma but not CSF, except for C3a which displayed greater sensitivity to FTs in CSF than in plasma. In CSF, the effect of FTs on C3a was reduced but not prevented by the supplementation with EDTA (±Futhan).

Conclusions

Our findings provide recommendations for CSF/plasma sample handling to ensure robust and reproducible complement biomarker analyses in AD.