TY - JOUR
T1 - Plasma and CSF neurofilament light
T2 - Relation to longitudinal neuroimaging and cognitive measures
AU - Mielke, Michelle M.
AU - Syrjanen, Jeremy A.
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Vemuri, Prashanthi
AU - Skoog, Ingmar
AU - Machulda, Mary M.
AU - Kremers, Walter K.
AU - Knopman, David S.
AU - Jack, Clifford
AU - Petersen, Ronald C.
AU - Kern, Silke
N1 - Funding Information:
This study was supported by funding from the NIH/ National Institute on Aging grants U01 AG006786, R01 AG011378, R01 AG041851, R01 AG049704, and R01 AG034676. Additional funding came from the GHR Foundation, the Swedish Research Council (2015-02,830), the European Research Council (681712), the Knut and Alice Wallenberg Foundation, Frimurarestiftelsen, the Olav Thon Foundation, Swedish State Support for Clinical Research (ALF Västra Götalandsregionen), the Swedish state under the agreement between the Swedish Government and the county councils, the ALF agreement (ALFGBG-813921, ALFGBG-65930, ALF-GBG-716681), the Tors-ten Söderberg Foundation, The Swedish Alzheimer Foundation, and Hjärnfonden Sweden.
Funding Information:
The Article Processing Charge was funded by the authors.
Funding Information:
M. Mielke served as a consultant to Eli Lilly and receives research support from the NIH and unrestricted research grants from Biogen and Lundbeck. J. Syrjanen reports no disclosures relevant to the manuscript. K. Blennow has served as a consultant or on advisory boards for Alzheon, CogRx, Biogen, Novartis, and Roche Diagnostics, and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg (not related to this study). H. Zetterberg has served on scientific advisory boards for Eli Lilly, Roche Diagnostics, Wave, Samumed, and CogRx; has received travel support
PY - 2019/7/16
Y1 - 2019/7/16
N2 - ObjectiveWe aimed to (1) assess and compare baseline plasma and CSF neurofilament light (NfL) for cross-sectional and longitudinal associations with neuroimaging or cognition and (2) determine whether change in plasma NfL corresponded with change in these outcomes.MethodsSeventy-nine participants without dementia, median age 76 years, had plasma and CSF NfL, neuropsychological testing, and neuroimaging (MRI, amyloid PET, FDG-PET) at the same study visit, and a repeat visit (15 or 30 months later) with both plasma NfL and neuroimaging. Plasma NfL was measured on the Simoa-HD1 Platform and CSF NfL with an in-house ELISA. Linear mixed effects models were used to examine the associations between baseline plasma or CSF NfL and cognitive and neuroimaging outcomes adjusting for age, sex, and education. The relationship between change in plasma NfL and change in the outcomes was assessed using linear regression.ResultsThere were no cross-sectional associations between CSF or plasma NfL and any neuroimaging or cognitive measure. Longitudinally, higher baseline plasma NfL was associated with worsening in all neuroimaging measures, except amyloid PET, and global cognition. Higher baseline CSF NfL was associated with worsening in cortical thickness and diffusion MRI. The beta estimates for CSF NfL were similar to those for plasma NfL. Change in plasma NfL was associated with change in global cognition, attention, and amyloid PET.ConclusionElevated baseline plasma NfL is a prognostic marker of cognitive decline and neuroimaging measures of neurodegeneration, and has similar effect sizes to baseline CSF NfL. Change in plasma NfL also tracked with short-Term cognitive change.
AB - ObjectiveWe aimed to (1) assess and compare baseline plasma and CSF neurofilament light (NfL) for cross-sectional and longitudinal associations with neuroimaging or cognition and (2) determine whether change in plasma NfL corresponded with change in these outcomes.MethodsSeventy-nine participants without dementia, median age 76 years, had plasma and CSF NfL, neuropsychological testing, and neuroimaging (MRI, amyloid PET, FDG-PET) at the same study visit, and a repeat visit (15 or 30 months later) with both plasma NfL and neuroimaging. Plasma NfL was measured on the Simoa-HD1 Platform and CSF NfL with an in-house ELISA. Linear mixed effects models were used to examine the associations between baseline plasma or CSF NfL and cognitive and neuroimaging outcomes adjusting for age, sex, and education. The relationship between change in plasma NfL and change in the outcomes was assessed using linear regression.ResultsThere were no cross-sectional associations between CSF or plasma NfL and any neuroimaging or cognitive measure. Longitudinally, higher baseline plasma NfL was associated with worsening in all neuroimaging measures, except amyloid PET, and global cognition. Higher baseline CSF NfL was associated with worsening in cortical thickness and diffusion MRI. The beta estimates for CSF NfL were similar to those for plasma NfL. Change in plasma NfL was associated with change in global cognition, attention, and amyloid PET.ConclusionElevated baseline plasma NfL is a prognostic marker of cognitive decline and neuroimaging measures of neurodegeneration, and has similar effect sizes to baseline CSF NfL. Change in plasma NfL also tracked with short-Term cognitive change.
UR - http://www.scopus.com/inward/record.url?scp=85069947956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069947956&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000007767
DO - 10.1212/WNL.0000000000007767
M3 - Article
C2 - 31182505
AN - SCOPUS:85069947956
VL - 93
SP - E252-E260
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 3
ER -