Variability in longitudinal cerebrospinal fluid tau and phosphorylated tau measurements

The influence of assay variation and duration of storage on changes in cerebrospinal fluid (CSF) levels of tau and phosphorylated (P)-tau with time was evaluated in 112 patients with various neurological disorders.

These patients (aged 66+/-9 years, 52% male), referred to our memory clinic, underwent two spinal taps (mean interval 19 months) and the baseline samples were assayed twice in a sandwich enzyme-linked immunosorbent assay (ELISA): once after the first spinal tap (A1) and once in a separately stored aliquot (A2) simultaneous with the follow-up sample (B).

Coefficients of variances (CVs) of tau and P-tau levels determined in repeated spinal taps (DeltaB-A2) measured in one assay (10.9% and 7.6%) were lower (p<0.01) than the CVs observed in two different (DeltaB-A1) assays (16.5% and 11.7%). The CVs of tau and P-tau measurement of one CSF sample repeated on two occasions (DeltaA1-A2) were 12.3% and 8.6%. A difference in mean P-tau level was found if the same CSF samples were repeatedly measured in two different ELISAs (A1-A2).

Longitudinal CSF tau and P-tau are best measured in one assay resulting in a lower variability compared to measurement in two different assays. The within person variability in levels of these markers currently limits the use of these ELISAs in a longitudinal clinical setting.