Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer’s disease
Abstract
Neurofilament light (NfL) is a marker of neuroaxonal injury, a prominent feature of Alzheimer’s disease. It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the Alzheimer’s disease continuum. The aim of this study was to investigate how plasma NfL relates to amyloid and tau PET and MRI measures of brain atrophy in participants with and without cognitive impairment. We retrospectively examined the association between plasma NfL and MRI measures of grey/white matter volumes in the Alzheimer’s Disease Neuroimaging Initiative [ADNI: n = 1149; 382 cognitively unimpaired control subjects and 767 cognitively impaired participants (mild cognitive impairment n = 420, Alzheimer’s disease dementia n = 347)]. Longitudinal plasma NfL was measured using single molecule array (Simoa) technology. Cross-sectional associations between plasma NfL and PET amyloid and tau measures were independently assessed in two cohorts: ADNI [n = 198; 110 cognitively unimpaired, 88 cognitively impaired (MCI n = 67, Alzheimer’s disease dementia n = 21), data accessed October 2018]; and Translational Biomarkers in Aging and Dementia [TRIAD, n = 116; 74 cognitively unimpaired, 42 cognitively impaired (MCI n = 16, Alzheimer’s disease dementia n = 26), data obtained November 2017 to January 2019]. Associations between plasma NfL and imaging-derived measures were examined voxel-wise using linear regression (cross-sectional) and linear mixed effect models (longitudinal). Cross-sectional analyses in both cohorts showed that plasma NfL was associated with PET findings in brain regions typically affected by Alzheimer’s disease; associations were specific to amyloid PET in cognitively unimpaired and tau PET in cognitively impaired (P < 0.05). Longitudinal analyses showed that NfL levels were associated with grey/white matter volume loss; grey matter atrophy in cognitively unimpaired was specific to APOE ε4 carriers (P < 0.05). These findings suggest that plasma NfL increases in response to amyloid-related neuronal injury in preclinical stages of Alzheimer’s disease, but is related to tau-mediated neurodegeneration in symptomatic patients. As such, plasma NfL may a useful measure to monitor effects in disease-modifying drug trials.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 19, 2020
- Source ID
- 10.1093/brain/awaa342
Entities
People
- Antoine Leuzy
- Aurelie Labbe
- Eduardo R. Zimmer
- For The Alzheimer’s Disease Neuroimaging Initiative*
- Henrik Zetterberg
- Joseph Therriault
- Kaj Blennow
- Melissa Savard
- Michael Schöll
- Min Su Kang
- Mira Chamoun
- Nicholas J. Ashton
- Pedro Rosa-Neto
- Serge Gauthier
- Sulantha Mathotaarachchi
- Tharick A Pascoal
Organizations
- AbbVie
- Alzheimer's Association
- Alzheimer's Disease Neuroimaging Initiative
- Alzheimer's Drug Discovery Foundation
- BioClinica
- Canada Foundation for Innovation
- Canadian Consortium on Neurodegeneration in Aging
- Canadian Institutes of Health Research
- European Research Council
- Federal University of Rio Grande do Sul
- Fonds de recherche du Québec
- HEC Montréal
- King's College London
- Lund University
- McGill University
- McGill University Health Centre
- National Institute of Biomedical Imaging and Bioengineering
- National Institute on Aging
- National Institutes of Health
- Northern California Institute for Research and Education
- Sahlgrenska University Hospital
- Swedish Research Council
- Torsten Söderberg Foundation
- United States Department of Defense
- University College London
- University of Gothenburg
- University of Southern California
- Wallenberg Centre for Molecular and Translational Medicine