Current biomarkers of neuronal damage in sporadic Creutzfeldt–Jakob disease (sCJD) require analysis of cerebrospinal fluid, which involves an invasive lumbar puncture procedure. However, a study has now shown that levels of tau and neurofilament light (NfL) are raised substantially in the serum of patients with sCJD. Investigators used an ultrasensitive single molecule array assay to monitor very low concentrations of these molecules in the blood. The team found that serum levels of NfL and tau enabled discrimination between healthy individuals and patients with sCJD with high sensitivity and specificity. Longitudinal analysis showed that levels of both proteins increased in patients with sCJD over time. Furthermore, serum levels of tau correlated positively with the rate of disease progression. These findings could facilitate early identification of patients with sCJD and provide useful outcome measures in future therapeutic trials.