PT  - JOURNAL ARTICLE
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
TI  - Plasma and CSF neurofilament light
AID  - 10.1212/WNL.0000000000007767
DP  - 2019 Jul 16
TA  - Neurology
PG  - e252--e260
VI  - 93
IP  - 3
4099  - http://n.neurology.org/content/93/3/e252.short
4100  - http://n.neurology.org/content/93/3/e252.full
SO  - Neurology2019 Jul 16; 93
AB  - Objective We 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.Methods Seventy-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.Results There 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.Conclusion Elevated 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.AD=Alzheimer disease; ADNI=Alzheimer's Dementia Neuroimaging Initiative; CU=cognitively unimpaired; DTI=diffusion tensor imaging; FA=fractional anisotropy; FDG=[18F]-fluorodeoxyglucose; MCI=mild cognitive impairment; MCSA=Mayo Clinic Study of Aging; NfL=neurofilament light; PiB=Pittsburgh compound B; REP=Rochester Epidemiology Project; SUVR=standardized uptake value ratio