Abstract
Neurofilament light chain (NFL) measurement has been gaining strong support as a clinically useful neuronal injury biomarker for various neurodegenerative conditions. However, in Alzheimer’s disease (AD), its reflection on regional neuronal injury in the context of amyloid pathology remains unclear. This study included 83 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 73 AD subjects who were further classified based on amyloid-beta (Aβ) status as positive or negative (Aβ+ vs Aβ−). In addition, 13 rats (5 wild type and 8 McGill-R-Thy1-APP transgenic (Tg)) were examined. In the clinical study, reduced precuneus/posterior cingulate cortex and hippocampal grey matter density were significantly associated with increased NFL concentrations in cerebrospinal fluid (CSF) or plasma in MCI Aβ+ and AD Aβ+. Moreover, AD Aβ+ showed a significant association between the reduced grey matter density in the AD-vulnerable regions and increased NFL concentrations in CSF or plasma. Congruently, Tg rats recapitulated and validated the association between CSF NFL and grey matter density in the parietotemporal cortex, entorhinal cortex, and hippocampus in the presence of amyloid pathology. In conclusion, reduced grey matter density and elevated NFL concentrations in CSF and plasma are associated in AD-vulnerable regions in the presence of amyloid positivity in the AD clinical spectrum and amyloid Tg rat model. These findings further support the NFL as a neuronal injury biomarker in the research framework of AD biomarker classification and for the evaluation of therapeutic efficacy in clinical trials.
Highlights
Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative database
In mild cognitive impairment (MCI) Aβ+ cases, increased cerebrospinal fluid (CSF) Neurofilament light chain (NFL) concentration was significantly associated with reduced Voxel-based morphometry (VBM) in the orbitofrontal cortex, lateral temporal cortex, precuneus/PCC, hippocampus and thalamus based on the voxel-based analysis (Fig. 4a and Supplementary Fig. 8 and Table 8)
NFL has been reported to be a novel neuronal injury or neurodegeneration biomarker but previous studies have only focused on the association between NFL concentrations and a priori regions of interest (ROI) volume over regions typically affected by Alzheimer’s disease (AD) [11, 17, 19]
Summary
Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative database (adni.loni.usc. edu). NFL elevation is an indicator of the presence of neurodegenerative processes, this fluid biomarker lacks the topographical information present in [18F]FDG-PET or MRI scans [21, 22] This is an important limitation since plasma or CSF NFL levels might reflect disease-specific grey or white matter neurodegenerative processes or diseaseindependent healthy aging process [22,23,24]. We illustrate voxel-based correlates between NFL and grey matter density maps in humans and McGill-Thy1-APP transgenic (Tg) rat model [25] This Tg model is ideal to study the effect Aβ alone as it progressively develops Aβ pathology comparable to AD Aβ pathology without the presence of tau pathology or minimal cell death [25,26,27]. The present study highlights that NFL concentration reflects neuronal injury processes in the regions that are vulnerable to AD in the presence of Aβ pathology
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
