Measurement batch differences and between‐batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values

Abstract

Abstract Introduction Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. Methods A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland‐Altman plot, paired t test, Pitman‐Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches. Results We found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R2 except for converting P‐tau between batches 1 and 3. Discussion Between‐batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers.

Keywords

• Alzheimer's disease
• batch difference
• biomarker
• cerebrospinal fluid
• conversion
• generalized linear model