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