TY - JOUR
T1 - Cerebrospinal Fluid Biomarkers in Autopsy-Confirmed Alzheimer Disease and Frontotemporal Lobar Degeneration
AU - Mattsson-Carlgren, Niklas
AU - Grinberg, Lea T.
AU - Boxer, Adam
AU - Ossenkoppele, Rik
AU - Jonsson, Magnus
AU - Seeley, William
AU - Ehrenberg, Alexander
AU - Spina, Salvatore
AU - Janelidze, Shorena
AU - Rojas-Martinex, Julio
AU - Rosen, Howard
AU - la Joie, Renaud
AU - Lesman-Segev, Orit
AU - Iaccarino, Leonardo
AU - Kollmorgen, Gwendlyn
AU - Ljubenkov, Peter
AU - Eichenlaub, Udo
AU - Gorno-Tempini, Maria Luisa
AU - Miller, Bruce
AU - Hansson, Oskar
AU - Rabinovici, Gil Dan
N1 - Funding Information: This work was partially funded by Roche Diagnostics (assay kits, materials, and employee salaries for U.E. and G.K). ELECSYS is a registered trademark of Roche. The Elecsys CSF Aβ, Aβ, P-tau, and T-tau immunoassays are not yet cleared or approved for clinical use in the United States. The NeuroToolKit robust prototype assays are for investigational purposes only and are not approved for clinical use. All other product names and trademarks are the property of their respective owners. Work at the authors' laboratory is funded by Knut and Alice Wallenberg Foundation, the Medical Faculty at Lund University, Region Skåne, the European Research Council, the Swedish Research Council, the Strategic Research Area MultiPark at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, The Parkinson Foundation of Sweden, The Parkinson Research Foundation, the Skåne University Hospital Foundation, the Swedish federal government under the ALF agreement, and the Bundy Academy. Work at UCSF was supported by NIH/National Institute on Aging grants (P30-AG062422, P01-AG019724, R01-AG038791, K08-AG052648, R01-NS050915, P50 AG023501, R01 AG045611, U19AG063911, K24053435, U54NS092089, R01AG031278, K99AG065501). 42 40 Funding Information: The Article Processing Charge was funded by the authors. Publisher Copyright: Copyright © 2022 The Author(s).
PY - 2022/3/15
Y1 - 2022/3/15
N2 - Background and Objectives To determine how fully automated Elecsys CSF immunoassays for β-amyloid (Aβ) and tau biomarkers and an ultrasensitive Simoa assay for neurofilament light chain (NFL) correlate with neuropathologic changes of Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). Methods We studied 101 patients with antemortem CSF and neuropathology data. CSF samples were collected a mean of 2.9 years before death (range 0.2–7.5 years). CSF was analyzed for Aβ 40, Aβ 42, total tau (T-tau), tau phosphorylated at amino acid residue 181 (P-tau), P-tau/Aβ 42 and Aβ 42/Aβ 40 ratios, and NFL. Neuropathology measures included Thal phases, Braak stages, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) scores, AD neuropathologic change (ADNC), and primary and contributory pathologic diagnoses. Associations between CSF biomarkers and neuropathologic features were tested in regression models adjusted for age, sex, and time from sampling to death. Results CSF biomarkers were associated with neuropathologic measures of Aβ (Thal, CERAD score), tau (Braak stage), and overall ADNC. The CSF P-tau/Aβ 42 and Aβ 42/Aβ 40 ratios had high sensitivity, specificity, and overall diagnostic performance for intermediate-high ADNC (area under the curve range 0.95–0.96). Distinct biomarker patterns were seen in different FTLD subtypes, with increased NFL and reduced P-tau/T-tau in FTLD–TAR DNA-binding protein 43 and reduced T-tau in progressive supranuclear palsy compared to other FTLD variants. Discussion CSF biomarkers, including P-tau, T-tau, Aβ 42, Aβ 40, and NFL, support in vivo identification of AD neuropathology and correlate with FTLD neuropathology.
AB - Background and Objectives To determine how fully automated Elecsys CSF immunoassays for β-amyloid (Aβ) and tau biomarkers and an ultrasensitive Simoa assay for neurofilament light chain (NFL) correlate with neuropathologic changes of Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). Methods We studied 101 patients with antemortem CSF and neuropathology data. CSF samples were collected a mean of 2.9 years before death (range 0.2–7.5 years). CSF was analyzed for Aβ 40, Aβ 42, total tau (T-tau), tau phosphorylated at amino acid residue 181 (P-tau), P-tau/Aβ 42 and Aβ 42/Aβ 40 ratios, and NFL. Neuropathology measures included Thal phases, Braak stages, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) scores, AD neuropathologic change (ADNC), and primary and contributory pathologic diagnoses. Associations between CSF biomarkers and neuropathologic features were tested in regression models adjusted for age, sex, and time from sampling to death. Results CSF biomarkers were associated with neuropathologic measures of Aβ (Thal, CERAD score), tau (Braak stage), and overall ADNC. The CSF P-tau/Aβ 42 and Aβ 42/Aβ 40 ratios had high sensitivity, specificity, and overall diagnostic performance for intermediate-high ADNC (area under the curve range 0.95–0.96). Distinct biomarker patterns were seen in different FTLD subtypes, with increased NFL and reduced P-tau/T-tau in FTLD–TAR DNA-binding protein 43 and reduced T-tau in progressive supranuclear palsy compared to other FTLD variants. Discussion CSF biomarkers, including P-tau, T-tau, Aβ 42, Aβ 40, and NFL, support in vivo identification of AD neuropathology and correlate with FTLD neuropathology.
UR - http://www.scopus.com/inward/record.url?scp=85126490649&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000200040
DO - https://doi.org/10.1212/WNL.0000000000200040
M3 - Article
C2 - 35173015
SN - 0028-3878
VL - 98
SP - e1137-e1150
JO - Neurology
JF - Neurology
IS - 11
ER -