Fig. 4

Measurement of soluble TREM2 in CSF from ALS patients and controls. Soluble TREM2 levels were measured by ELISA in CSF from ALS patients (n = 46) and controls (n = 20) who were age and sex matched. Levels of soluble TREM2 are significantly higher in ALS patients compared to controls (Mann–Whitney, p < 0.05) (a). Stage of ALS at the time of sample was determined by the time from onset to sample compared to time from onset to death (censored). Levels of soluble TREM2 are highest in early ALS (CSF sampled in <25th centile of disease course), intermediately raised in late (>75th centile of disease course) and lowest in controls (b). Error bars show standard error. Levels of soluble TREM2 are positively correlated with disease duration in late stage ALS (c). We suggest a model whereby CSF soluble TREM2 is elevated in early disease in all ALS patients but then gradually reduces. In certain patients levels remain relatively high reflecting a prolonged neuroprotective microglial activation which leads to slower disease progression (d)