Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease

Alzheimers Res Ther. 2018 Jul 28;10(1):71. doi: 10.1186/s13195-018-0404-9.

Abstract

Background: A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer's disease (AD).

Methods: With a single molecule array method (Simoa, Quanterix), plasma NfL concentrations were measured in 99 subjects with AD at the stage of mild cognitive impairment (MCI-AD; n = 25) or at the stage of early dementia (ADD; n = 33), and in nondemented controls (n = 41); in all patients, the clinical diagnoses were in accordance with the results of the four core cerebrospinal fluid (CSF) biomarkers (amyloid β (Aβ)1-42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm. The influence of preanalytical storage procedures on the NfL in plasma was tested on samples exposed to six different conditions.

Results: NfL concentrations significantly increased in the samples exposed to more than one freezing/thawing cycle, and in those stored for 5 days at room temperature or at 4 °C. Compared with the control group of nondemented subjects (22.0 ± 12.4 pg/mL), the unadjusted plasma NfL concentration was highly significantly higher in the MCI-AD group (38.1 ± 15.9 pg/mL, p < 0.005) and even further elevated in the ADD group (49.1 ± 28.4 pg/mL; p < 0.001). A significant association between NfL and age (ρ = 0.65, p < 0.001) was observed; after correcting for age, the difference in NfL concentrations between AD and controls remained significant (p = 0.044). At the cutoff value of 25.7 pg/mL, unconditional sensitivity, specificity, and accuracy were 0.84, 0.78, and 0.82, respectively. Unadjusted correlation between plasma NfL and Mini Mental State Examination (MMSE) across all patients was moderate but significant (r = -0.49, p < 0.001). We observed an overall significant correlation between plasma NfL and the CSF biomarkers, but this correlation was not observed within the diagnostic groups.

Conclusions: This study confirms increased concentrations of plasma NfL in patients with Alzheimer's disease compared with nondemented controls.

Keywords: Alzheimer’s disease; Biomarker; Neurofilament light; Plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Female
  • Humans
  • Male
  • Mental Status Schedule
  • Microarray Analysis
  • Middle Aged
  • Nerve Degeneration / blood*
  • Nerve Degeneration / cerebrospinal fluid
  • Nerve Degeneration / etiology*
  • Neurofilament Proteins / blood*
  • Peptide Fragments / cerebrospinal fluid
  • ROC Curve

Substances

  • Amyloid beta-Peptides
  • Neurofilament Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • neurofilament protein L