Amyloid-beta modulates the association between neurofilament light chain and brain atrophy in Alzheimer's disease.

TitleAmyloid-beta modulates the association between neurofilament light chain and brain atrophy in Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2020
AuthorsKang MSu, Aliaga AAliaga, Shin M, Mathotaarachchi S, Benedet AL, Pascoal TA, Therriault J, Chamoun M, Savard M, Devenyi GA, Mathieu A, Chakravarty MM, Sandelius Å, Blennow K, Zetterberg H, Soucy J-P, A Cuello C, Massarweh G, Gauthier S, Rosa-Neto P
Corporate AuthorsAlzheimer’s Disease Neuroimaging Initiative
JournalMol Psychiatry
Date Published2020 Jun 26
ISSN1476-5578
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.

DOI10.1038/s41380-020-0818-1
Alternate JournalMol Psychiatry
PubMed ID32591633
Grant ListNIRP-12-259245 / / Alzheimer's Association / United States
#2018-02532 / / Vetenskapsrådet (Swedish Research Council) /
2016PJT-364544 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /