Uncovering proteostasis biology causing Alzheimer’s Disease using AMP‐AD transcriptomic data
Year: 2023
Type: article
Abstract: Background Proteostasis biology is the network of various pathways associated with protein homeostasis and malfunction, which is the major cause of developing various neurodegenerative diseases like Alzheimer’s Disease. Recently, Accelerated‐Medicine Partnership – Alzheimer’s Disease consortia has released a huge amount of OMICS data generated by thousands of post‐mortem brains from various cohorts. Such data provides excellent opportunities to gain insight about proteostasis pathway network crosstalk behind Alzheimer’s Disease. As a part of early discovery initiatives using transcriptomic bulk RNA‐seq data derived from post‐mortem brain, AMP‐AD consortia published data‐driven identification of 30 network modules that are supposed to capture disease biology unbiased to any hypothesis. These modules are thousands of genes co‐expressed in the population in various conditions robust to any computational methods, batch effect of cohort‐specific effects. Method We explored these AMP‐AD modules from the proteostasis perspective by identifying proteostasis relevant network modules published from AMP‐AD and further integrating additional omics data and network properties to identify candidates associated with Alzheimer’s Disease pathology. We hypothesize that these candidates could be tested for early validation as potential drug targets. Result Our analysis shows that proteostasis is one of the major underlying mechanisms confounded in most of the network module. However, certain modules are more enriched for proteostasis‐relevant pathways, suggesting their role in disease progression. Furthermore, some of the proposed candidates are known to be involved in the disease, indicating utility of this analysis providing additional candidates for early validation towards AD therapeutics. Conclusion AMP‐AD transcriptomic data analysis provides significant insight on proteostasis biology causing Alzheimer’s Disease.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.062625
Author: Dong Xu
Institution: University of Missouri
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4380880467