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

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 HanssonGil Dan Rabinovici

Research output: Contribution to JournalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)e1137-e1150
JournalNeurology
Volume98
Issue number11
DOIs
Publication statusPublished - 15 Mar 2022

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