■阿尔茨海默病(AD)是一种常见的神经退行性疾病,具有多步骤的疾病进展。AD的中度和晚期之间的差异尚未完全表征。
■这里,我们在454个AD相关样本中进行了转录-分辨率分析,包括145个非痴呆控制,140无症状AD(AsyAD),和169个AD样本。我们在转录水平比较地表征了AsymAD和AD样品中的转录组失调。
■我们确定了4,056和1,200个差异剪接的选择性剪接事件(ASEs),它们可能在AsyAD和AD的疾病进展中起作用。分别。我们的进一步分析揭示了在AsyAD和AD中的287和222个同工型转换事件,分别。特别是,共有163份和119份成绩单显示使用量增加,124和103个转录本在AsymAD和AD中的使用减少,分别。例如,基因APOA2在AD和非痴呆对照样品之间没有表达变化,但与非痴呆对照样品相比,AD中转录物ENST00000367990.3的比例较高,转录物ENST00000463812.1的比例较低。此外,我们构建了RNA结合蛋白(RBP)-ASE调节网络,以揭示AsyAD和AD中潜在的RBP介导的同工型开关。
■总之,我们的研究提供了对AsymAD和AD转录组干扰的转录分辨率的见解,这将促进AD患者早期诊断生物标志物的发现和新的治疗策略的发展。
UNASSIGNED: Alzheimer\'s disease (AD) is a common neurodegenerative disorder that has a multi-step disease progression. Differences between moderate and advanced stages of AD have not yet been fully characterized.
UNASSIGNED: Herein, we performed a transcript-resolution analysis in 454 AD-related samples, including 145 non-demented control, 140 asymptomatic AD (AsymAD), and 169 AD samples. We comparatively characterized the transcriptome dysregulation in AsymAD and AD samples at transcript level.
UNASSIGNED: We identified 4,056 and 1,200 differentially spliced alternative splicing events (ASEs) that might play roles in the disease progression of AsymAD and AD, respectively. Our further analysis revealed 287 and 222 isoform switching events in AsymAD and AD, respectively. In particular, a total of 163 and 119 transcripts showed increased usage, while 124 and 103 transcripts exhibited decreased usage in AsymAD and AD, respectively. For example, gene APOA2 showed no expression changes between AD and non-demented control samples, but expressed higher proportion of transcript ENST00000367990.3 and lower proportion of transcript ENST00000463812.1 in AD compared to non-demented control samples. Furthermore, we constructed RNA binding protein (RBP)-ASE regulatory networks to reveal potential RBP-mediated isoform switch in AsymAD and AD.
UNASSIGNED: In summary, our study provided transcript-resolution insights into the transcriptome disturbance of AsymAD and AD, which will promote the discovery of early diagnosis biomarkers and the development of new therapeutic strategies for patients with AD.