Journal
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
Volume 11, Issue 1, Pages 679-689Publisher
WILEY
DOI: 10.1016/j.dadm.2019.08.002
Keywords
Neurofilament light; Hypometabolism; [F-18]FDG; Neurodegeneration; Alzheimer's disease; Biomarkers; Blood; PET; Longitudinal
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [MOP-11-51-31]
- Alzheimer's Association [NIRG-08-92090]
- Canadian Consortium of Neurodegeneration in Aging (CIHR-CCNA)
- Weston Brain Institute
- CAPES Foundation-Brazil [0327/13-1]
- Wallenberg Center for Molecular and Translational Medicine
- Torsten Soderberg Foundation, Stockholm, Swe-den
- CAPES [88881.141186/201701]
- CNPq [460172/2014-0]
- FAPERGS/CNPq [16/2551-0000475-7]
- Brazilian National Institute of Science and Technology in Excitotoxicity and Neuroprotection [465671/2014-4]
- FAPERGS/MS/CNPq/SESRSPPSUS [30786.434.24734.23112017]
- Swedish Research Council [2018-02532]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- UK Dementia Research Institute at UCL
- Fonds de la recherche en sant~e du Qu~ebec (chercheur boursier)
- MRC [UKDRI-1003] Funding Source: UKRI
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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.
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