CSF biomarkers of Alzheimer’s disease concord with amyloid-β PETand predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts

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-β(1–42) (Aβ), total tau/Aβ(1–42), and phosphorylated tau/Aβ(1–42) were defined against [(18)F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [(18)F]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.