Alina Bauer, Christina Rabe, Courtney Schiffman, Fiona Rose, Gesine Respondek, Fabiana Gullotta, Laura Schlieker, Alexander Jethwa, Isabelle Schrurs, Ekaterina Manuilova, Susanne Ostrowitzki, Tobias Bittner
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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.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>BBBM pre-screening in SKYLINE using prototype plasma pTau181 and ApoE4p immunoassays effectively alleviated participant burden by avoiding unnecessary PET or CSF testing.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>We compared blood-based biomarker (BBBM) performance in SKYLINE and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4).</li>\n \n <li>Pre-screening improved amyloid positivity (defined by positron emission tomography/cerebrospinal fluid) screen failure rate.</li>\n \n <li>Tau phosphorylated at threonine 181 (pTau181) and apolipoprotein E4 protein was the highest-performing combination among BBBMs tested.</li>\n \n <li>Pre-screening eased participant burden by reducing subsequent screening procedures.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519518/pdf/","citationCount":"0","resultStr":"{\"title\":\"Blood-based pre-screening in the SKYLINE secondary prevention Ph3 gantenerumab study\",\"authors\":\"Alina Bauer, Christina Rabe, Courtney Schiffman, Fiona Rose, Gesine Respondek, Fabiana Gullotta, Laura Schlieker, Alexander Jethwa, Isabelle Schrurs, Ekaterina Manuilova, Susanne Ostrowitzki, Tobias Bittner\",\"doi\":\"10.1002/alz.70676\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>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<sup>®</sup> plasma immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland).</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>In >3500 participants screened in SKYLINE, tau phosphorylated at threonine 181 (pTau181) and apolipoprotein E4 protein (ApoE4p) was the highest-performing BBBM combination. 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Blood-based pre-screening in the SKYLINE secondary prevention Ph3 gantenerumab study
INTRODUCTION
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.
METHODS
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).
RESULTS
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.
DISCUSSION
BBBM pre-screening in SKYLINE using prototype plasma pTau181 and ApoE4p immunoassays effectively alleviated participant burden by avoiding unnecessary PET or CSF testing.
Highlights
We compared blood-based biomarker (BBBM) performance in SKYLINE and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4).
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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