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CDiP 技术用于散发性阿尔茨海默病的逆向工程。

CDiP technology for reverse engineering of sporadic Alzheimer's disease.

机构信息

Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.

Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan.

出版信息

J Hum Genet. 2023 Mar;68(3):231-235. doi: 10.1038/s10038-022-01047-8. Epub 2022 Jun 10.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that causes cognitive impairment for which neither treatable nor preventable approaches have been confirmed. Although genetic factors are considered to contribute to sporadic AD, for the majority of AD patients, the exact causes of AD aren't fully understood. For AD genetics, we developed cellular dissection of polygenicity (CDiP) technology to identify the smallest unit of AD, i.e., genetic factors at a cellular level. By CDiP, we found potential therapeutic targets, a rare variant for disease stratification, and polygenes to predict real-world AD by using the real-world data of AD cohort studies (Alzheimer's Disease Neuroimaging Initiative: ADNI and Japanese Alzheimer's Disease Neuroimaging Initiative: J-ADNI). In this review, we describe the components and results of CDiP in AD, induced pluripotent stem cell (iPSC) cohort, a cell genome-wide association study (cell GWAS), and machine learning. And finally, we discuss the future perspectives of CDiP technology for reverse engineering of sporadic AD toward AD eradication.

摘要

阿尔茨海默病(AD)是一种神经退行性疾病,可导致认知障碍,目前既没有可治疗的方法,也没有可预防的方法。虽然遗传因素被认为与散发性 AD 有关,但对于大多数 AD 患者,AD 的确切病因尚未完全了解。对于 AD 遗传学,我们开发了多基因遗传的细胞剖析(CDiP)技术,以确定 AD 的最小单位,即在细胞水平上的遗传因素。通过 CDiP,我们发现了潜在的治疗靶点、用于疾病分层的罕见变异体以及多基因,这些可以通过 AD 队列研究的真实世界数据(阿尔茨海默病神经影像学倡议:ADNI 和日本阿尔茨海默病神经影像学倡议:J-ADNI)来预测真实世界中的 AD。在这篇综述中,我们描述了 CDiP 在 AD 中的组成部分和结果、诱导多能干细胞(iPSC)队列、细胞全基因组关联研究(cell GWAS)和机器学习。最后,我们讨论了 CDiP 技术用于散发性 AD 反向工程以实现 AD 消除的未来展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266c/9968655/23651a8e6223/10038_2022_1047_Fig1_HTML.jpg

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