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Randomized Controlled Trial
. 2023 Aug;19(8):3379-3388.
doi: 10.1002/alz.12919. Epub 2023 Feb 16.

CSF biomarker concordance with amyloid PET in Phase 3 studies of aducanumab

Laura Nisenbaum  1 , Robert Martone  1 , Tianle Chen  1 , Rajasimhan Rajagovindan  1 , Gersham Dent  1 , John Beaver  1 , Carrie Rubel  1 , Annie Racine  1 , Ping He  1 , Katie Harrison  1 , Robert Dean  2   3 , Manu Vandijck  4 , Samantha Budd Haeberlein  1
Affiliations
Randomized Controlled Trial

CSF biomarker concordance with amyloid PET in Phase 3 studies of aducanumab

Laura Nisenbaum et al. Alzheimers Dement. 2023 Aug.

Abstract

Introduction: We assessed the use of cerebrospinal fluid (CSF) biomarkers as an alternative to positron emission tomography (PET) for brain amyloid beta (Aβ) pathology confirmation in the EMERGE and ENGAGE clinical trials.

Methods: EMERGE and ENGAGE were randomized, placebo-controlled, Phase 3 trials of aducanumab in participants with early Alzheimer's disease. Concordance between CSF biomarkers (Aβ42, Aβ40, phosphorylated tau 181, and total tau) and amyloid PET status (visual read) at screening was examined.

Results: Robust concordance between CSF biomarkers and amyloid PET visual status was observed (for Aβ42/Aβ40, AUC: 0.90; 95% CI: 0.83-0.97; p < 0.0001), confirming CSF biomarkers as a reliable alternative to amyloid PET in these studies. Compared with single CSF biomarkers, CSF biomarker ratios showed better agreement with amyloid PET visual reads, demonstrating high diagnostic accuracy.

Discussion: These analyses add to the growing body of evidence supporting CSF biomarkers as reliable alternatives to amyloid PET imaging for brain Aβ pathology confirmation.

Highlights: CSF biomarkers and amyloid PET concordance were assessed in Ph3 aducanumab trials. Robust concordance between CSF biomarkers and amyloid PET was observed. CSF biomarker ratios increased diagnostic accuracy over single CSF biomarkers. CSF Aβ42/Aβ40 demonstrated high concordance with amyloid PET. Results support CSF biomarker testing as a reliable alternative to amyloid PET.

Keywords: Alzheimer's disease; EMERGE; ENGAGE; amyloid beta; biomarker; cerebrospinal fluid; concordance analysis; positron emission tomography; tau.

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