Cerebrospinal Fluid Biomarkers in Autopsy-Confirmed Alzheimer Disease and Frontotemporal Lobar Degeneration

著者: Niklas Mattsson-Carlgren, Lea T. Grinberg, Adam Boxer, Rik Ossenkoppele, Magnus Jonsson, William Seeley, Alexander Ehrenberg, Salvatore Spina, Shorena Janelidze, Julio Rojas-Martinex, Howard Rosen, Renaud La Joie, Orit Lesman-Segev, Leonardo Iaccarino, Gwendlyn Kollmorgen, Peter Ljubenkov, Udo Eichenlaub, Maria Luisa Gorno-Tempini, Bruce Miller, Oskar Hansson, Gil Dan Rabinovici - Neurology 2022 被引用: 130

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: 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: 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: , and NFL, support in vivo identification of AD neuropathology and correlate with FTLD neuropathology. CLASSIFICATION OF EVIDENCE: , and NFL, are associated with AD and FTLD neuropathology.