Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

ABSTRACT:

Background

Cerebrospinal fluid (CSF) biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD).

Objective

We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation.

Methods

We measured CSF amyloid-? (A?) 1-42, total tau (t-tau), and phosphorylated tau (p-tau) by INNOTEST enzyme-linked-immunosorbent assays (ELISA) in a memory clinic population (n?=?126). Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern.

Results

CSF intralaboratory variability was higher for A?1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal) of 26% of the subjects based on A?1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for A?1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on A?1-42, 1% based on t-tau, and 22% based on p-tau.

Conclusions

Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for A?1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

SUBMITTER: Vos SJ 

PROVIDER: S-EPMC4069102 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature