Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease - PubMed (original) (raw)

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

Piotr Lewczuk et al. Alzheimers Res Ther. 2018.

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.

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Conflict of interest statement

The ethical committee of the University of Erlangen-Nuremberg approved the study, and all patients or their caregivers gave their written consent.

Not applicable.

Competing interests

PL has received consultation and/or lecture honoraria from IBL International, Fujirebio Europe, AJ Roboscreen, and Roche. KB has served as a consultant or on advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics. KB and HZ are cofounders of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. HZ has served on advisory boards of Eli Lilly and Roche Diagnostics and has received travel support from Teva. CS and JP are full-time employees of Boehringer Ingelheim. All remaining authors declare that they have no competing interests.

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Figures

Fig. 1

Fig. 1

Neurofilament light chain (NfL) plasma levels of samples with different preanalytical treatment. *p < 0.05, versus the reference (Ref.) sample (frozen at −80 °C and unthawed). d days, F/T freeze/thaw cycle, n.s. not significant, RT room temperature

Fig. 2

Fig. 2

Unadjusted neurofilament light chain (NfL) concentrations in the three diagnostic categories. A borderline insignificant (p = 0.11 after Scheffe correction) tendency was observed towards higher concentrations in Alzheimer’s disease dementia (ADD) compared with mild cognitive impairment Alzheimer’s disease (MCI-AD). The green horizontal line represents the cutoff at the maximized Youden index (25.7 pg/mL), leading to the unadjusted diagnostic accuracy of 82% in the setting of controls versus AD (MCI-AD and ADD). *p < 0.05

Fig. 3

Fig. 3

Neurofilament light chain (NfL) plasma levels plotted against age in nondemented controls (green) and the AD patients (a combined group of MCI-AD and ADD subjects, red). The black dotted line represents the optimal separation of the two groups according to Fisher’s LDA

Fig. 4

Fig. 4

a Unadjusted ROC curve in the setting of controls vs. AD. b Sensitivity (blue), specificity (brown), and accuracy (green) as functions of age. AUC area under the curve, CI confidence interval, SE standard error

Fig. 5

Fig. 5

Correlation between plasma neurofilament light chain (NfL) concentrations and the Mini Mental State Examination (MMSE) results

Fig. 6

Fig. 6

Plasma neurofilament light chain (NfL) plotted against cerebrospinal fluid (CSF) Tau. a. Overall moderate, highly significant correlation between plasma NfL and CSF Tau; lacking within-group correlation between plasma NfL and CSF Tau in the controls (b), MCI-AD (c), and ADD (d)

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