Edmarie Guzmán-Vélez1, Henrik Zetterberg2,3,4,5, Joshua T Fox-Fuller1,6, Clara Vila-Castelar1, Justin S Sanchez1, Ana Baena7, Gloria Garcia-Ospina7, David Aguillon7, Enmanuelle Pardilla-Delgado1, Jennifer R Gatchel1,8, Reisa A Sperling1,9, Keith Johnson1,9, Eric M Reiman10,11,12,13, Kaj Blennow2,3, Francisco Lopera7, Yakeel T Quiroz1,7. 1. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 3. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal Campus, Mölndal, Sweden. 4. UK Dementia Research Institute at UCL, London, UK. 5. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 6. Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts, USA. 7. Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, Colombia. 8. Division of Geriatric Psychiatry and Psychiatric Neurotherapeutics, McLean Hospital, Belmont, Massachusetts, USA. 9. Brigham and Women's Hospital, Boston, Massachusetts, USA. 10. Banner Alzheimer's Institute, Phoenix, Arizona, USA. 11. University of Arizona, Phoenix, Arizona, USA. 12. Arizona State University, Phoenix, Arizona, USA. 13. Translational Genomics Research Institute, Phoenix, Arizona, USA.
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.
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.
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