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It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the Alzheimer\u2019s 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\u2019s Disease Neuroimaging Initiative [ADNI: n\u2009=\u20091149;\u00a0382 cognitively unimpaired control subjects and 767 cognitively impaired participants (mild cognitive impairment n\u2009=\u2009420, Alzheimer\u2019s disease dementia n\u2009=\u2009347)]. 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\u2009=\u2009198; 110 cognitively unimpaired, 88 cognitively impaired (MCI n\u2009=\u200967, Alzheimer\u2019s disease dementia n\u2009=\u200921), data accessed October 2018]; and Translational Biomarkers in Aging and Dementia [TRIAD, n\u2009=\u2009116;\u00a074 cognitively unimpaired, 42 cognitively impaired (MCI n\u2009=\u200916, Alzheimer\u2019s disease dementia n\u2009=\u200926), 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\u2019s disease; associations were specific to amyloid PET in cognitively unimpaired and tau PET in cognitively impaired (P\u2009&amp;lt;\u20090.05). Longitudinal analyses showed that NfL levels were associated with grey\/white matter volume loss; grey matter atrophy in cognitively unimpaired was specific to APOE \u03b54 carriers (P\u2009&amp;lt;\u20090.05). These findings suggest that plasma NfL increases in response to amyloid-related neuronal injury in preclinical stages of Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.1093\/brain\/awaa342","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T21:15:16Z","timestamp":1601414116000},"page":"3793-3804","source":"Crossref","is-referenced-by-count":123,"title":["Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9057-8014","authenticated-orcid":false,"given":"Andr\u00e9a L","family":"Benedet","sequence":"first","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"},{"name":"CAPES Foundation, Ministry of Education of Brazil, Bras\u00edlia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Leuzy","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences, Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharick A","family":"Pascoal","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"},{"name":"King\u2019s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK"},{"name":"NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulantha","family":"Mathotaarachchi","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Savard","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-4781","authenticated-orcid":false,"given":"Joseph","family":"Therriault","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Su","family":"Kang","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Chamoun","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00f6ll","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences, Malm\u00f6, Lund University, Lund, Sweden"},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo R","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, McGill University, Montreal, QC, Canada"},{"name":"Departament of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Labbe","sequence":"additional","affiliation":[{"name":"Department of Decision Sciences, HEC Montreal, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"},{"name":"UK Dementia Research Institute at UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Rosa-Neto","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada"},{"name":"Alzheimer\u2019s Disease Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, McGill University, Montreal, QC, Canada"},{"name":"Montreal Neurological Institute, Montreal, QC, Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging 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