Michelle M Mielke1,2, Scott A Przybelski1, Timothy G Lesnick1, Silke Kern3, Henrik Zetterberg3,4,5,6, Kaj Blennow3,4, David S Knopman2, Jonathan Graff-Radford2, Ronald C Petersen1,2, Clifford R Jack7, Prashanthi Vemuri7. 1. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. 2. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA. 3. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 4. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 5. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 6. UK Dementia Research Institute at UCL, London, UK. 7. Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
INTRODUCTION: We determined whether cerebrospinal fluid (CSF) neurofilament light (NfL), neurogranin (Ng), and total-tau (t-tau) differentially mapped to magnetic resonance imaging (MRI) measures of cortical thickness, microstructural integrity (corpus callosum and cingulum fractional anisotropy [FA]), and white matter hyperintensities (WMH). METHODS: Analyses included 536 non-demented Mayo Clinic Study of Aging participants with CSF NfL, Ng, t-tau, amyloid beta (Aβ)42 and longitudinal MRI scans. Linear mixed models assessed longitudinal associations between CSF markers and MRI changes. RESULTS: Higher CSF NfL was associated with decreasing microstructural integrity and WMH. Higher t-tau was associated with decreasing temporal lobe and Alzheimer's disease (AD) meta region of interest (ROI) cortical thickness. There was no association between Ng and any MRI measure. CSF Aβ42 interacted with Ng for declines in temporal lobe and AD meta ROI cortical thickness and cingulum FA. DISCUSSION: CSF NfL predicts changes in white matter integrity, t-tau reflects non-specific changes in cortical thickness, and Ng reflects AD-specific synaptic and neuronal degeneration.
INTRODUCTION: We determined whether cerebrospinal fluid (CSF) neurofilament light (NfL), neurogranin (Ng), and total-tau (t-tau) differentially mapped to magnetic resonance imaging (MRI) measures of cortical thickness, microstructural integrity (corpus callosum and cingulum fractional anisotropy [FA]), and white matter hyperintensities (WMH). METHODS: Analyses included 536 non-demented Mayo Clinic Study of Aging participants with CSF NfL, Ng, t-tau, amyloid beta (Aβ)42 and longitudinal MRI scans. Linear mixed models assessed longitudinal associations between CSF markers and MRI changes. RESULTS: Higher CSF NfL was associated with decreasing microstructural integrity and WMH. Higher t-tau was associated with decreasing temporal lobe and Alzheimer's disease (AD) meta region of interest (ROI) cortical thickness. There was no association between Ng and any MRI measure. CSF Aβ42 interacted with Ng for declines in temporal lobe and AD meta ROI cortical thickness and cingulum FA. DISCUSSION: CSF NfL predicts changes in white matter integrity, t-tau reflects non-specific changes in cortical thickness, and Ng reflects AD-specific synaptic and neuronal degeneration.
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