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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, neurodegeneration. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders are characterized by neuronal impairment that eventually leads to neuronal death. In spite of the brain’s known capacity for regeneration, lost neurons are difficult to replace. Therefore, drugs aimed at inhibiting neurodegenerative processes are likely to be most effective if the treatment is initiated as early as possible. However, clinical manifestations in early disease stages are often numerous, subtle and difficult to diagnose. This is where biomarkers that specifically reflect onset of pathology, directly or indirectly, may have a profound impact on diagnosis making in the future. A triplet of biomarkers for Alzheimer’s disease (AD), total and hyperphosphorylated tau and the 42 amino acid isoform of β-amyloid, has already been established for early detection of AD before the onset of dementia. However, more biomarkers are needed both for AD and for other neurodegenerative disorders, such as Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis. This review provides an update on recent advances in clinical neuroproteomics, a biomarker discovery field that has expanded immensely during the last decade, and gives an overview of the most commonly used techniques and the major clinically relevant findings these techniques have lead to. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which clarifies the benefits of using biomarker-assisted diagnosis-making in patients with genetic and cerebrospinal fluid (CSF) biomarker data to determine the pathology for Alzheimers's disease.