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

Artikel i vetenskaplig tidskrift
Författare M. S. Kang
A. A. Aliaga
M. Shin
S. Mathotaarachchi
A. L. Benedet
T. A. Pascoal
J. Therriault
M. Chamoun
M. Savard
G. A. Devenyi
A. Mathieu
M. M. Chakravarty
Åsa P Sandelius
Kaj Blennow
Henrik Zetterberg
J. P. Soucy
A. C. Cuello
G. Massarweh
S. Gauthier
P. Rosa-Neto
Neuroimaging Alzheimer's Dis
Publicerad i Molecular Psychiatry
Sidor 13
ISSN 1359-4184
Publiceringsår 2020
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 13
Språk en
Länkar dx.doi.org/10.1038/s41380-020-0818-...
Ämnesord transgenic rat model, cerebrospinal-fluid, neurodegenerative diseases, protein, progression, hypothesis, intensity, marker, blood, serum, Biochemistry & Molecular Biology, Neurosciences & Neurology, Psychiatry
Ämneskategorier Neurovetenskaper

Sammanfattning

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 (A beta) status as positive or negative (A beta+ vs A beta-). 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 A beta+ and AD A beta+. Moreover, AD A beta+ 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.

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