Transcriptional Landscape for Endoplasmic Reticulum Stress in Alzheimer's Disease Patients-Derived Dermal Fibroblast. Transcriptional Landscape for Endoplasmic Reticulum Stress in Alzheimer's Disease Patients-Derived Dermal Fibroblast

Numerous studies have identified various risk factors associated with Alzheimer's disease (AD). However, the experimental limitations of disease modeling make it challenging to directly interpret these effects. These limitations include constraints of postmortem samples, animal experiments, and challenges associated with brain tissue studies. Ex-vivo experiments effectively address these issues by enabling patient-specific identification and highlighting potential biomarkers. In addition, patient-derived human dermal fibroblast effectively reflect the molecular anomalies that disrupt cellular homeostasis. This study aimed to use an ex-vivo platform to characterize the transcriptional profile of fibroblasts derived from patients with AD in response to endoplasmic reticulum (ER) stress and propose potential biomarkers. We utilized patient-derived fibroblasts to observe differentially responsive genes to ER stress in both healthy controls (N=22) and patients with AD (N=20) using RNA sequencing. Overall design: All participants were enrolled in the BICWALZS. It was launched in October 2016 by the Korea Disease Control and Prevention Agency and is part of the National Korea Biobank Project conducted at Ajou University Hospital. Participants were classified into healthy control and AD groups based on specific criteria. we mimicked the ER stress environment in vitro by treating cells with thapsigargin at concentrations that allowed for cell survival. Transcriptomic analysis of thapsigargin treated and non-treated fibroblast by Bulk RNA sequencing

诸多研究已明确与阿尔茨海默病（Alzheimer's Disease, AD）相关的多种风险因素。然而，疾病建模的实验局限性使得直接阐释这些风险因素的作用机制颇具挑战。此类局限性包括尸检样本的取材限制、动物实验的固有缺陷，以及脑组织研究面临的诸多难题。离体（ex-vivo）实验可有效规避上述问题，能够实现患者特异性的靶点识别，并助力潜在生物标志物的发掘。此外，源自患者的人皮肤成纤维细胞可有效反映破坏细胞稳态的分子异常情况。本研究旨在借助离体实验平台，对阿尔茨海默病患者来源的成纤维细胞在内质网应激（endoplasmic reticulum, ER）刺激下的转录组特征进行表征，并挖掘潜在生物标志物。本研究利用患者来源的成纤维细胞，通过RNA测序技术，分析健康对照组（N=22）与阿尔茨海默病患者组（N=20）在内质网应激刺激下的差异响应基因。实验整体设计：所有受试者均纳入BICWALZS队列。该队列由韩国疾病管理厅（Korea Disease Control and Prevention Agency）于2016年10月启动，是韩国国立生物银行项目在亚洲大学附属医院（Ajou University Hospital）开展的子研究。研究人员依据特定标准将受试者划分为健康对照组与阿尔茨海默病患者组。本研究通过采用可维持细胞存活浓度的毒胡萝卜素处理细胞，在体外模拟内质网应激环境。本研究通过批量RNA测序（Bulk RNA sequencing），对毒胡萝卜素处理组与未处理组的成纤维细胞开展转录组分析。