Enrichment for clinical trials of early AD: Combining genetic risk factors and plasma p-tau as screening instruments

IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-10-23 DOI:10.1002/alz.14284
Xin Wang, Xinran Wang, Steven D. Edland, Iris J. Broce, Anders M. Dale, Sarah J. Banks, for the Alzheimer's Disease Neuroimaging Initiative
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Abstract

INTRODUCTION

Identifying low-cost, minimally-invasive screening instruments for Alzheimer's disease (AD) trial enrichment will improve the efficiency of AD trials.

METHODS

A total of 685 cognitively normal (CN) individuals and individuals with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were grouped according to cutoffs of genetic risk factor (G) polygenic hazard score (PHS) and tau pathology (T) plasma phosphorylated tau-181 (p-tau181) into four groups: G+T+, G-T-, G+T-, and G-T+. We assessed the associations between group level and longitudinal cognitive decline and AD conversion. Power analyses compared the estimated sample size required to detect differences in cognitive decline.

RESULTS

The G+T+ group was associated with faster cognitive decline and higher AD risk. Clinical trials enrolling G+T+ participants would benefit from significantly reduced sample sizes compared with similar trials using only single makers as an inclusion criterion.

DISCUSSION

The combination of two low-cost, minimally-invasive measures—genetics and plasma biomarkers—would be a promising screening procedure for clinical trial enrollment.

Highlights

  • Participants with unimpaired or mildly impaired cognition were grouped based on cutoffs on genetic risk factors (G: polygenic hazardous score [PHS]) and Alzheimer's pathology (T: baseline plasma phosphorylated tau-181 [p-tau181]).
  • Participants with high PHSs and plasma p-tau181 levels (G+T+) were at risk of faster cognitive decline and AD progression.
  • The combination of PHS and plasma p-tau181 could enhance clinical trial enrichment more effectively than using single biomarkers.

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丰富早期 AD 临床试验:结合遗传风险因素和血浆 p-tau 作为筛查工具
为阿尔茨海默病(AD)试验浓缩确定低成本、微创的筛查工具将提高AD试验的效率。
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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
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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