@article{36f502bbff9c483bacfbf7e166872460,
title = "Comparison of CSF neurofilament light chain, neurogranin, and tau to MRI markers",
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.",
keywords = "Alzheimer's, amyloid, cerebrospinal fluid, cohort study, cortical thickness, magnetic resonance imaging, neurodegeneration, neurofilament light chain, neurogranin, total tau, white matter integrity",
author = "Mielke, {Michelle M.} and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Silke Kern and Henrik Zetterberg and Kaj Blennow and Knopman, {David S.} and Jonathan Graff-Radford and Petersen, {Ronald C.} and Jack, {Clifford R.} and Prashanthi Vemuri",
note = "Funding Information: This study was supported by funding from the National Institutes of Health/National Institute on Aging grants U01 AG006786, P30 AG062677, R01 AG011378, R01 AG041851, and R01 AG034676. Additional funding came from the GHR Foundation, the Swedish Research Council (2015‐02830,2019‐02075), the European Research Council (681712), the Knut and Alice Wallenberg Foundation, Frimurarestiftelsen, the Olav Thon Foundation, Swedish State Support for Clinical Research (ALF V{\"a}stra G{\"o}talandsregionen), the Swedish state under the agreement between the Swedish Government and the county councils, the ALF‐agreement (ALFGBG‐813921, ALFGBG‐65930, ALF‐GBG‐716681,ALF GBG‐715986), the Torsten S{\"o}derberg Foundation, The Swedish Alzheimer Foundation, Hj{\"a}rnfonden Sweden, Stiftelsen Demensfonden, Stiftelsen Hjalmar Svenssons Forskningsfond, Stiftelsen Wilhelm och Martina Lundgrens Vetenskapsfond. HZ is a Wallenberg Scholar. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: This study was supported by funding from the National Institutes of Health/National Institute on Aging grants U01 AG006786, P30 AG062677, R01 AG011378, R01 AG041851, and R01 AG034676. Additional funding came from the GHR Foundation, the Swedish Research Council (2015-02830,2019-02075), the European Research Council (681712), the Knut and Alice Wallenberg Foundation, Frimurarestiftelsen, the Olav Thon Foundation, Swedish State Support for Clinical Research (ALF V?stra G?talandsregionen), the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-813921, ALFGBG-65930, ALF-GBG-716681,ALF GBG-715986), the Torsten S?derberg Foundation, The Swedish Alzheimer Foundation, Hj?rnfonden Sweden, Stiftelsen Demensfonden, Stiftelsen Hjalmar Svenssons Forskningsfond, Stiftelsen Wilhelm och Martina Lundgrens Vetenskapsfond. HZ is a Wallenberg Scholar. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: Dr. Mielke served as a consultant to Brain Protection Company and receives research support from the National Institutes of Health (R01 AG49704, P50 AG44170, U01 AG06786, RF1 AG55151), and unrestricted research grants from Biogen. Mr. Syrjanen has nothing to disclose. Mr. Przybelski and Mr. Lesnick have nothing to disclose. Dr. Kern has nothing to disclose. Dr. Zetterberg has served on advisory boards for Denali, CogRx, Roche Diagnostics, Samumed, and Wave; has given lectures in symposia sponsored by Fujirebio, Alzecure, and Biogen; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures‐based platform company at the University of Gothenburg. Dr. Blennow has served as a consultant or on advisory boards for Alzheon, Axon Neuroscience, Biogen, Eli Lilly, MagQu, Novartis, and Roche Diagnostics, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures‐based platform company at the University of Gothenburg. Dr. Knopman serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the Alzheimer's Disease Cooperative Study; and receives research support from the National Institutes of Health. Dr. Graff‐Radford has nothing to disclose. Dr. Petersen is a consultant for Roche, Inc., Merck, Inc., Biogen, Inc., Genentech, Inc., Eisai, Inc., and GE Healthcare. He receives research support from the National Institutes of Health. Dr. Jack has provided consulting services for Eli Lilly. He receives research funding from the National Institutes of Health, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Dr. Vemuri has nothing to disclose. Publisher Copyright: {\textcopyright} 2020 the Alzheimer's Association",
year = "2021",
month = may,
doi = "10.1002/alz.12239",
language = "English (US)",
volume = "17",
pages = "801--812",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "5",
}