Michelle M Mielke1, Jeremy A Syrjanen2, Kaj Blennow3, Henrik Zetterberg4, Ingmar Skoog5, Prashanthi Vemuri6, Mary M Machulda7, Jonathan Graff-Radford8, David S Knopman8, Clifford R Jack6, Ronald C Petersen9, Silke Kern10. 1. Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: Mielke.Michelle@mayo.edu. 2. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. 3. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 4. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL (H.Z.), London, UK. 5. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. 6. Department of Radiology, Mayo Clinic, Rochester, MN, USA. 7. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. 8. Department of Neurology, Mayo Clinic, Rochester, MN, USA. 9. Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. 10. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Abstract
INTRODUCTION: Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total-tau [T-tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging-Alzheimer's Association Research Framework. METHODS: We examined, in a community-based population (N = 777, aged 50-95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays. RESULTS: Multiple variables were differentially associated with CSF NfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in the presence of amyloidosis, followed by Ng. Variables associations with NfL did not differ by amyloid status. DISCUSSION: Understanding factors that influence CSF (N) markers will assist in the interpretation and utility of these markers in clinical practice.
INTRODUCTION: Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total-tau [T-tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging-Alzheimer's Association Research Framework. METHODS: We examined, in a community-based population (N = 777, aged 50-95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays. RESULTS: Multiple variables were differentially associated with CSFNfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in the presence of amyloidosis, followed by Ng. Variables associations with NfL did not differ by amyloid status. DISCUSSION: Understanding factors that influence CSF (N) markers will assist in the interpretation and utility of these markers in clinical practice.
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