Volume 17, Issue 5 p. 813-821
FEATURED ARTICLE

Associations between plasma neurofilament light, in vivo brain pathology, and cognition in non-demented individuals with autosomal-dominant Alzheimer's disease

Edmarie Guzmán-Vélez

Edmarie Guzmán-Vélez

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Henrik Zetterberg

Henrik Zetterberg

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal Campus, Mölndal, Sweden

UK Dementia Research Institute at UCL, London, UK

Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK

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Joshua T. Fox-Fuller

Joshua T. Fox-Fuller

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts, USA

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Clara Vila-Castelar

Clara Vila-Castelar

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Justin S. Sanchez

Justin S. Sanchez

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Ana Baena

Ana Baena

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, Colombia

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Gloria Garcia-Ospina

Gloria Garcia-Ospina

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, Colombia

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David Aguillon

David Aguillon

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, Colombia

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Enmanuelle Pardilla-Delgado

Enmanuelle Pardilla-Delgado

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Jennifer R. Gatchel

Jennifer R. Gatchel

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Division of Geriatric Psychiatry and Psychiatric Neurotherapeutics, McLean Hospital, Belmont, Massachusetts, USA

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Reisa A. Sperling

Reisa A. Sperling

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Brigham and Women's Hospital, Boston, Massachusetts, USA

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Keith Johnson

Keith Johnson

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Brigham and Women's Hospital, Boston, Massachusetts, USA

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Eric M. Reiman

Eric M. Reiman

Banner Alzheimer's Institute, Phoenix, Arizona, USA

University of Arizona, Phoenix, Arizona, USA

Arizona State University, Phoenix, Arizona, USA

Translational Genomics Research Institute, Phoenix, Arizona, USA

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Kaj Blennow

Kaj Blennow

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal Campus, Mölndal, Sweden

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Francisco Lopera

Francisco Lopera

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, Colombia

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Yakeel T. Quiroz

Corresponding Author

Yakeel T. Quiroz

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, Colombia

Correspondence

Yakeel T. Quiroz, PhD, Associate Professor, Harvard Medical School, Departments of Psychiatry and Neurology, Massachusetts General Hospital, 100 1st Avenue, Building 39, Suite 101, Charlestown, MA 02129, USA

Email: [email protected]

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First published: 01 February 2021
Citations: 6

Abstract

Background

Neurofilament light (NfL) is a promising biomarker of early neurodegeneration in Alzheimer's disease (AD). We examined whether plasma NfL was associated with in vivo amyloid beta and tau, and cognitive performance in non-demented presenilin-1 (PSEN1) E280A mutation carriers.

Methods

Twenty-five mutation carriers and 19 non-carriers (age range: 28 to 49 years) were included in this study. Participants underwent 11C Pittsburgh compound B (PiB)-PET (positron emission tomography), flortaucipir–PET, blood sampling, and cognitive testing.

Results

Mutation carriers exhibited higher plasma NfL levels than non-carriers. In carriers, higher NfL levels were related to greater regional tau burden and worse cognition, but not amyloid beta load. When we adjusted for age, a proxy of disease progression, elevated plasma NfL levels were only correlated with worse memory recall.

Conclusions

Findings support an association between plasma NfL, cognition, and tau pathology in non-demented individuals at genetic risk for developing AD dementia. Plasma NfL may be useful for selecting individuals at increased risk and tracking disease progression in AD.

CONFLICTS OF INTEREST

All other co-authors have no conflicts or disclosures relevant to the manuscript.