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

被引：31

作者：

Kang, Min Su ^{[1
,2
,3
]}

Aliaga, Arturo Aliaga ^{[1
,2
,3
]}

Shin, Monica ^{[1
,2
]}

Mathotaarachchi, Sulantha ^{[1
,2
]}

Benedet, Andrea L. ^{[1
,2
]}

Pascoal, Tharick A. ^{[1
,2
]}

Therriault, Joseph ^{[1
,2
]}

Chamoun, Mira ^{[1
,2
]}

Savard, Melissa ^{[1
,2
]}

Devenyi, Gabriel A. ^{[2
,4
]}

Mathieu, Axel ^{[2
]}

Chakravarty, M. Mallar ^{[2
,4
,5
]}

Sandelius, Asa ^{[6
]}

Blennow, Kaj ^{[6
,7
]}

Zetterberg, Henrik ^{[6
,7
,8
,9
]}

Soucy, Jean-Paul ^{[3
]}

Cuello, A. Claudio ^{[10
]}

Massarweh, Gassan ^{[3
]}

Gauthier, Serge ^{[1
,2
,3
]}

Rosa-Neto, Pedro ^{[1
,2
,3
,4
]}

机构：

[1] McGill Univ, Translat Neuroimaging Lab, Res Ctr Studying Aging, Montreal, PQ, Canada

[2] Douglas Res Ctr, Cerebral Imaging Ctr, Montreal, PQ, Canada

[3] McGill Univ, McConnell Brain Imaging Ctr, Montreal, PQ, Canada

[4] McGill Univ, Dept Psychiat, Montreal, PQ, Canada

[5] McGill Univ, Dept Biomed Engn, Montreal, PQ, Canada

[6] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Molndal, Sweden

[7] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[8] UCL, UK Dementia Res Inst, London, England

[9] UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England

[10] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada

来源：

MOLECULAR PSYCHIATRY | 2021年 / 26卷 / 10期

基金：

加拿大健康研究院; 英国医学研究理事会; 瑞典研究理事会; 美国国家卫生研究院; 欧洲研究理事会;

关键词：

TRANSGENIC RAT MODEL; CEREBROSPINAL-FLUID; NEURODEGENERATIVE DISEASES; PROTEIN; PROGRESSION; HYPOTHESIS; INTENSITY; MARKER; BLOOD; SERUM;

D O I：

10.1038/s41380-020-0818-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：5989 / 6001

页数：13

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