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弥合差距:多民族人群中阿尔茨海默病患者和老年对照者脑组织的多组学分析。

Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer's disease and older controls in multi-ethnic populations.

机构信息

Mayo Clinic Florida, Jacksonville, Florida, USA.

Sage Bionetworks, Seattle, Washington, USA.

出版信息

Alzheimers Dement. 2024 Oct;20(10):7174-7192. doi: 10.1002/alz.14208. Epub 2024 Aug 30.

Abstract

INTRODUCTION

Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD.

METHODS

To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors.

RESULTS

We generated multi-omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non-Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures.

DISCUSSION

The inclusion of traditionally underrepresented groups in multi-omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.

HIGHLIGHTS

Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi-ethnic populations. Brain multi-omics data is generated from Black American, Latin American, and non-Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.

摘要

简介

阿尔茨海默病(AD)的多组学研究揭示了许多潜在的疾病途径和治疗靶点。尽管这些研究有望实现精准医疗,但它们缺乏受 AD 影响不成比例的黑人和拉丁裔美国人(BA 和 LA)。

方法

为了弥补这一差距,阿尔茨海默病加速药物研发伙伴关系(AMP-AD)将大脑多组学分析扩展到多种族供体。

结果

我们生成了多组学数据,并对来自 BA(n=306)、LA(n=326)或 BA 和 LA(n=4)脑供体的表型数据进行了整理和协调,加上非西班牙裔白人(n=252)和其他(n=20)族裔群体,建立了一个富含 BA 和 LA 参与者的基础数据集。本研究描述了可供研究社区使用的数据,包括来自三个大脑区域的转录组、全基因组序列和蛋白质组测量。

讨论

在多组学研究中纳入传统上代表性不足的群体对于发现将与所有受 AD 影响的人群相关的精准医疗靶点的全貌至关重要。

重点

阿尔茨海默病加速药物研发伙伴关系多样性倡议领导了多民族人群的脑组织分析。从黑人和拉丁裔美国人和非西班牙裔白人供体中产生了大脑多组学数据。完成并共享 RNA、全基因组测序和串联质量标签蛋白质组学。对包括尾状核、颞叶和背外侧前额叶皮层在内的多个大脑区域进行了分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/575b/11485084/ee26950a0f4a/ALZ-20-7174-g001.jpg

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