eprintid: 10051921 rev_number: 29 eprint_status: archive userid: 608 dir: disk0/10/05/19/21 datestamp: 2018-07-12 10:40:23 lastmod: 2021-09-17 22:09:23 status_changed: 2019-06-24 12:49:23 type: article metadata_visibility: show creators_name: Hansson, O creators_name: Seibyl, J creators_name: Stomrud, E creators_name: Zetterberg, H creators_name: Trojanowski, JQ creators_name: Bittner, T creators_name: Lifke, V creators_name: Corradini, V creators_name: Eichenlaub, U creators_name: Batrla, R creators_name: Buck, K creators_name: Zink, K creators_name: Rabe, C creators_name: Blennow, K creators_name: Shaw, LM creators_name: Swedish BioFINDER study group, . creators_name: Alzheimer's Disease Neuroimaging Initiative, . title: CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Amyloid PET concordance, Amyloid-β (1–42), Biomarker validation, CSF biomarkers, Clinical progression, Cutoffs, Phosphorylated tau (pTau), Total tau (tTau) note: Copyright © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). abstract: INTRODUCTION: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. METHODS: Cutoffs for Elecsys amyloid-β1-42 (Aβ), total tau/Aβ(1-42), and phosphorylated tau/Aβ(1-42) were defined against [18F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. RESULTS: CSF total tau/Aβ(1-42) and phosphorylated tau/Aβ(1-42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%-90%; area under the curves: 96%) and predicted greater 2-year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read-based outcomes. DISCUSSION: Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis. date: 2018-11 date_type: published official_url: https://doi.org/10.1016/j.jalz.2018.01.010 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1541282 doi: 10.1016/j.jalz.2018.01.010 pii: S1552-5260(18)30029-3 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Cuccu, Clara actors_id: CCCUC40 actors_role: owner full_text_status: public publication: Alzheimer's & Dementia volume: 14 number: 11 pagerange: 1470-1481 event_location: United States issn: 1552-5279 citation: Hansson, O; Seibyl, J; Stomrud, E; Zetterberg, H; Trojanowski, JQ; Bittner, T; Lifke, V; ... Alzheimer's Disease Neuroimaging Initiative, .; + view all <#> Hansson, O; Seibyl, J; Stomrud, E; Zetterberg, H; Trojanowski, JQ; Bittner, T; Lifke, V; Corradini, V; Eichenlaub, U; Batrla, R; Buck, K; Zink, K; Rabe, C; Blennow, K; Shaw, LM; Swedish BioFINDER study group, .; Alzheimer's Disease Neuroimaging Initiative, .; - view fewer <#> (2018) CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimer's & Dementia , 14 (11) pp. 1470-1481. 10.1016/j.jalz.2018.01.010 <https://doi.org/10.1016/j.jalz.2018.01.010>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10051921/14/Zetterberg%20VoR%201-s2.0-S1552526018300293-main.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/10051921/8/1-s2.0-S1552526018300293-mmc1.pdf