Plasma and cerebrospinal fluid tau and neurofilament concentrations in rapidly progressive neurological syndromes: a neuropathology-based cohort

Background and purpose: Cerebrospinal fluid (CSF) tau and neurofilament light chain (NF‐L) proteins have proved to be reliable biomarkers for neuronal damage; however, there is a strong need for blood‐based tests. Methods: The present study included 132 autopsy cases with rapidly progressive neurological syndromes, including Alzheimer disease (AD) (21), sporadic (65) and genetic (21) Creutzfeldt–Jakob disease (CJD), 25 cases with vascular, neoplastic and inflammatory alterations, and additionally 18 healthy control individuals. CSF tau and NF‐L concentrations were measured by enzyme‐linked immunosorbent assay. Plasma tau and NF‐L concentrations were measured using ultra‐sensitive single molecule array technology. Results: Plasma and CSF tau (R = 0.59, P < 0.001) and NF‐L (R = 0.69, P < 0.001) levels correlated significantly (Spearman test). Plasma tau and NF‐L levels were significantly higher in all disease groups compared to healthy controls (P < 0.001). Receiver operating characteristic curves were used and area under the curve values for comparisons with controls were 0.82 (AD), 0.94 (sporadic CJD), 0.92 (genetic CJD) and 0.83 (other neurological disorders) for plasma tau and 0.99, 0.99, 1.00 and 0.96 for plasma NF‐L, respectively. Molecular subtyping of sporadic CJD showed a strong effect (linear logistic regression) on plasma tau (P < 0.001) but not NF‐L levels (P = 0.19). Conclusion: Plasma tau and NF‐L concentrations are strongly increased in CJD and show similar diagnostic performance to the corresponding CSF measure. Molecular subtypes of sporadic CJD show different levels of plasma tau. Although not disease‐specific, these findings support the use of plasma tau and NF‐L as tools to identify, or to rule out, neurodegeneratio