Diagnostic accuracy of CSF neurofilament light chain protein in the biomarker-guided classification system for Alzheimer's disease

- The diagnostic accuracy of NFL protein in cerebrospinal fluid is examined.
- A biomarker-based descriptive stratification model for AD is used.
- NFL protein discriminates AD pathophysiology from HCs with fair diagnostic accuracy.
- The ability of NFL protein in differentiating tau-positive patients from HCs is poor.
- The ability of NFL in distinguishing AD pathophysiology from FTD is unsatisfactory.

We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein in the classification of patients with Alzheimer's disease (AD) and cognitively healthy control individuals (HCs) and patients with frontotemporal dementia (FTD) as comparisons. Particularly, we tested the performance of CSF NFL concentration in differentiating patient groups stratified by fluid biomarker profiles, independently of the severity of cognitive impairment (mild cognitive impairment (MCI) and AD dementia individuals), using a biomarker-guided descriptive classification system for AD. CSF NFL concentrations were examined in a multicenter cross-sectional study of 108 participants stratified in AD pathophysiology-negative (both CSF tau and the 42-amino acid-long amyloid-beta (Aβ) peptide (Aβ1-42)) (n = 15), tau pathology-positive only (n = 15), Aβ pathology-positive only (n = 13), AD pathophysiology-positive (n = 33), FTD (n = 9) patients, and HCs (n = 23), according to the biomarker-based classification system. The performance of CSF NFL in discriminating AD pathophysiology-positive patients from HCs is fair, whereas the ability in differentiating tau-positive patients from HCs is poor. The classificatory performance in distinguishing AD pathophysiology-positive patients from FTD is unsatisfactory.