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

Andréa L Benedet; Nicholas J Ashton; Tharick A Pascoal; Antoine Leuzy; Sulantha Mathotaarachchi; Min S Kang; Joseph Therriault; Melissa Savard; Mira Chamoun; Michael Schöll; Eduardo R Zimmer; Serge Gauthier; Aurélie Labbe; Henrik Zetterberg; Kaj Blennow; Pedro R Neto

doi:10.1016/j.dadm.2019.08.002

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

Alzheimers Dement (Amst). 2019 Sep 27:11:679-689. doi: 10.1016/j.dadm.2019.08.002. eCollection 2019 Dec.

Authors

Andréa L Benedet^{1

2}, Nicholas J Ashton^{3

4

5

6}, Tharick A Pascoal¹, Antoine Leuzy⁷, Sulantha Mathotaarachchi¹, Min S Kang¹, Joseph Therriault¹, Melissa Savard¹, Mira Chamoun¹, Michael Schöll^{3

4

7

8}, Eduardo R Zimmer^{9

10}, Serge Gauthier⁹, Aurélie Labbe¹¹, Henrik Zetterberg^{3

12

13

14}, Kaj Blennow^{3

12}, Pedro R Neto^{1

15

16}

Affiliations

¹ Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada.
² CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁵ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
⁶ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁷ Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
⁸ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁹ Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, McGill University, Montreal, Quebec, Canada.
¹⁰ Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
¹¹ Department of Decision Sciences, HEC Montreal, Montreal, Quebec, Canada.
¹² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹³ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹⁴ UK Dementia Research Institute at UCL, London, UK.
¹⁵ Montreal Neurological Institute, Montreal, Quebec, Canada.
¹⁶ Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

Abstract

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 [¹⁸F]fluorodeoxyglucose ([¹⁸F]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 [¹⁸F]FDG in amyloid positive (Aβ+) and negative (Aβ-) subjects.

Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [¹⁸F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [¹⁸F]FDG-NfL were confined to cognitively impaired Aβ+ individuals.

Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.

Keywords: Alzheimer's disease; Biomarkers; Blood; Hypometabolism; Longitudinal; Neurodegeneration; Neurofilament light; PET; [18F]FDG.

Abstract

Grants and funding