Amyotrophic lateral sclerosis: disease stage related changes of biochemical markers (tau protein, creatine kinase, sCD14) in CSF and serum

Objective: Recently, we found CSF tau protein and serum creatine kinase (CK) concentration changes related to the stage of the disease in a smaller series of 20 patients with Amyotrophic lateral sclerosis (ALS). Furthermore, several studies have demonstrated the presence of inflammatory infiltrates containing macrophages within the spinal cord of ALS patients. One possibility to monitor the macrophage activity could be the determination of the phagocyte activation marker soluble CD14 (sCD14). We aimed to analyse CSF tau protein, serum CK and CSF sCD14 in a larger cohort of ALS patients.

Methods: Paired CSF and serum samples of 90 patients (27 female, 63 male, mean age 59 years +/- 12.0 years) with sporadic ALS were obtained. As a control group, CSF and serum samples of 30 age-matched healthy persons were analysed. Tau, CK and sCD14 were determined using commercially available ELISA kits. Statistical analysis was carried out using Mann-Whitney U-test.

Results: Compared to age-related normal reference ranges, CSF tau was found to be increased in 63% of all ALS cases. Tau values were highest at early disease stages with a mean concentration of 302 ng/L, followed by a continuous decrease of tau over the course of the disease. Serum CK showed elevated levels in 56% of patients exceeding the upper reference level up to the 4.9-fold. Mean sCD14 levels in CSF were 426.4 ng/ml compared to 511.7 ng/ml of healthy controls (p=0.017) with a slight non-significant decrease with increasing disease duration (p=0.11).

Conclusion: Considering the individually different disease courses our data suggest a specific pattern of tau concentration changes related to disease stage. Elevated CSF tau indicating neuronal damage and increased serum CK reflecting muscle injury suggest a specific relation between neuronal and muscular damage, which is in accordance to the pathophysiological processes in which neuronal degeneration precedes muscle cell degeneration. The dynamic of tau concentration may reflect the activity of the neuronal degeneration in regions adjacent to the CSF compartment.

Decreased sCD14 levels suggest reduced macrophage activity in patients with ALS vs. controls. Whether this finding is of pathophysiologic relevance, e.g. relationship between inflammation and neurodegeneration, remains to be further analysed.