Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals

被引:58
作者
Benedet, Andrea L. [1 ,2 ]
Ashton, Nicholas J. [3 ,4 ,5 ,6 ]
Pascoal, Tharick A. [1 ]
Leuzy, Antoine [7 ]
Mathotaarachchi, Sulantha [1 ]
Kang, Min S. [1 ]
Therriault, Joseph [1 ]
Savard, Melissa [1 ]
Chamoun, Mira [1 ]
Schoell, Michael [3 ,4 ,7 ,8 ]
Zimmer, Eduardo R. [9 ,10 ]
Gauthier, Serge [9 ]
L'abbe, Aurelie [11 ]
Zetterberg, Henrik [3 ,12 ,13 ,14 ]
Blennow, Kaj [3 ,12 ]
Neto, Pedro R. [1 ,15 ,16 ]
机构
[1] McGill Univ, McGill Ctr Studies Aging, Translat Neuroimaging Lab, Montreal, PQ, Canada
[2] Minist Educ Brazil, CAPES Fdn, Brasilia, DF, Brazil
[3] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
[4] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
[5] Kings Coll London, Inst Psychiat Psychol & Neurosci, Clin Neurosci Inst, Maurice Wohl Inst, London, England
[6] South London & Maudsley NHS Fdn, NIHR Biomed Res Ctr Mental Hlth & Biomed, Res Unit Dementia, London, England
[7] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden
[8] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England
[9] McGill Univ, McGill Univ Res Ctr Studies Aging, Alzheimers Dis Res Unit, Montreal, PQ, Canada
[10] Univ Fed Rio Grande do Sul, Dept Pharmacol, Porto Alegre, RS, Brazil
[11] HEC Montreal, Dept Decis Sci, Montreal, PQ, Canada
[12] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
[13] UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England
[14] UCL, UK Dementia Res Inst, London, England
[15] Montreal Neurol Inst, Montreal, PQ, Canada
[16] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada
基金
加拿大健康研究院; 瑞典研究理事会; 欧洲研究理事会;
关键词
Neurofilament light; Hypometabolism; F-18]FDG; Neurodegeneration; Alzheimer's disease; Biomarkers; Blood; PET; Longitudinal;
D O I
10.1016/j.dadm.2019.08.002
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [F-18]fluorodeoxyglucose ([F-18]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [F-18]FDG in amyloid positive (A beta+) and negative (A beta-) subjects. Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [F-18]FDG uptake in correspondent brain regions. In A beta+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [F-18]FDG-NfL were confined to cognitively impaired A beta+ individuals. Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in A beta+ subjects. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
引用
收藏
页码:679 / 689
页数:11
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