Blood‐based pre‐screening in the SKYLINE secondary prevention Ph3 gantenerumab study

TL;DR

Blood-based biomarkers like pTau181 and ApoE4p can effectively pre-screen participants for amyloid positivity, reducing the need for PET or CSF tests.

Contribution

The study identifies the best-performing blood-based biomarker combination for pre-screening in Alzheimer's prevention trials.

Findings

pTau181 and ApoE4p were the highest-performing blood-based biomarker combination in pre-screening.

Clinical performance matched predictions from the A4 study in terms of screen-out rate and predictive values.

Pre-screening reduced participant burden by avoiding unnecessary PET or CSF testing.

Abstract

SKYLINE was a secondary prevention study that used blood‐based biomarker (BBBM) pre‐screening to screen out participants with a low likelihood of amyloid positivity by positron emission tomography (PET) or cerebrospinal fluid (CSF) testing.

This retrospective analysis used data from SKYLINE (ClinicalTrials.gov: NCT05256134; terminated prematurely) and the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4) study to compare predicted and actual clinical performance characteristics of various biomarker combinations using prototype Elecsys® plasma immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland).

In >3500 participants screened in SKYLINE, tau phosphorylated at threonine 181 (pTau181) and apolipoprotein E4 protein (ApoE4p) was the highest‐performing BBBM combination. Actual clinical performance of the BBBM pre‐screening in SKYLINE was similar to predictions based on A4 in terms of screen‐out rate, positive predictive value, and 1‐negative predictive value.

BBBM pre‐screening in SKYLINE using prototype plasma pTau181 and ApoE4p immunoassays effectively alleviated participant burden by avoiding unnecessary PET or CSF testing.

We compared blood‐based biomarker (BBBM) performance in SKYLINE and Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4).Pre‐screening improved amyloid positivity (defined by positron emission tomography/cerebrospinal fluid) screen failure rate.Tau phosphorylated at threonine 181 (pTau181) and apolipoprotein E4 protein was the highest‐performing combination among BBBMs tested.Pre‐screening eased participant burden by reducing subsequent screening procedures.

We compared blood‐based biomarker (BBBM) performance in SKYLINE and Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4).

Pre‐screening improved amyloid positivity (defined by positron emission tomography/cerebrospinal fluid) screen failure rate.

Tau phosphorylated at threonine 181 (pTau181) and apolipoprotein E4 protein was the highest‐performing combination among BBBMs tested.

Pre‐screening eased participant burden by reducing subsequent screening procedures.

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