Publications & Posters

Short-term biological variation of serum glial fibrillary acidic protein

Clinical Chemistry and Laboratory Medicine | August 15, 2022

Christensen, S. H., Hviid, C. V. B., Madsen, A. T., Parkner, T. and Winther-Larsen, A.

Clin Chem Lab Med, vol. 60, no. 11, 2022, pp. 1813-1819

This study was performed using the Quanterix HD-1 Analyzer.



Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker for intracerebral diseases and is approved for clinical use in traumatic brain injury. GFAP is also being investigated for several other applications, where the GFAP changes are not always outstanding. It is thus essential for the interpretation of GFAP to distinguish clinical relevant changes from natural occurring biological variation. This study aimed at estimating the biological variation of serum GFAP.


Apparently healthy subjects (n=33) had blood sampled for three consecutive days. On the second day, blood was also drawn every third hour from 9 AM to 9 PM. Serum GFAP was measured by Single Molecule Array (Simoa™). Components of biological variation were estimated in a linear mixed-effects model.


The overall median GFAP value was 92.5 pg/mL (range 34.4–260.3 pg/mL). The overall within– (CVI) and between-subject variations (CVG) were 9.7 and 39.5%. The reference change value was 36.9% for an increase. No day-to-day variation was observed, however semidiurnal variation was observed with increasing GFAP values between 9 AM and 12 PM (p<0.00001) and decreasing from 12 to 9 PM (p<0.001).


Serum GFAP exhibits a relatively low CVI but a considerable CVG and a marked semidiurnal variation. This implies caution on the timing of blood sampling and when interpreting GFAP in relation to reference intervals, especially in conditions where only small GFAP differences are observed.