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

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-β _1–42 (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.