Skip to main content

Alzheimer's Disease

Transcriptome analysis of early- and late-onset Alzheimer's disease in Korean cohorts



INTRODUCTION


The molecular mechanisms underlying early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) remain incompletely understood, particularly in Asian populations.

METHODS


RNA-sequencing was carried out on blood samples from 248 participants in the Seoul National University Bundang Hospital cohort to perform differential gene expression (DGE) and weighted gene co-expression network analysis. Findings were replicated in an independent Korean cohort (N = 275).

RESULTS


DGE analysis identified 18 and 88 dysregulated genes in EOAD and LOAD, respectively. Network analysis identified a LOAD-associated module showing a significant enrichment in pathways related to mitophagy, 5′ adenosine monophosphate-activated protein kinase signaling, and ubiquitin-mediated proteolysis. In the replication cohort, downregulation of SMOX and PLVAP in LOAD was replicated, and the LOAD-associated module was highly preserved. In addition, SMOX and PLVAP were associated with brain amyloid beta deposition.

DISCUSSION


Our findings suggest distinct molecular signatures for EOAD and LOAD in a Korean population, providing deeper understanding of their diagnostic potential and molecular mechanisms.

Analysis identified 18 and 88 dysregulated genes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD), respectively. Expression levels of SMOX and PLVAP were downregulated in LOAD. Expression levels of SMOX and PLVAP were associated with brain amyloid beta deposition. Pathways including mitophagy and 5′ adenosine monophosphate-activated protein kinase signaling were enriched in a LOAD module. A LOAD module was highly preserved across two independent cohorts.

Comments

Post a Comment

Popular posts from this blog

Fruitful innovation

Fruitful innovation: Transforming watermelon genetics with advanced base editors The development of new adenine base editors (ABE) and adenine-to-thymine/ guanine base editors (AKBE) is transforming watermelon genetic engineering. These innovative tools enable precise A:T-to-G and A:T-to-T base substitutions, allowing for targeted genetic modifications. The research highlights the efficiency of these editors in generating specific mutations, such as a flowerless phenotype in ClFT (Y84H) mutant plants. This advancement not only enhances the understanding of gene function but also significantly improves molecular breeding, paving the way for more efficient watermelon crop improvement. Traditional breeding methods for watermelon often face challenges in achieving desired genetic traits efficiently and accurately. While CRISPR/Cas9 has provided a powerful tool for genome editing, its precision and scope are sometimes limited. These limitations highlight the need for more advanced gene-e...
Post a Comment
Read more

Genetic factors with clinical trial stoppage

Genetic factors associated with reasons for clinical trial stoppage Many drug discovery projects are started but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the free-text reasons for 28,561 clinical trials that stopped before their endpoints were met. We then evaluated these classes in light of the underlying evidence for the therapeutic hypothesis and target properties. We found that trials are more likely to stop because of a lack of efficacy in the absence of strong genetic evidence from human populations or genetically modified animal models. Furthermore, certain trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is broadly expressed across tissues. These results support the growing use of human genetics to ...
Post a Comment
Read more

Asexual Ants maintain Genetic Diversity

How do asexual ants maintain genetic diversity? It’s commonly accepted wisdom that genetic diversity is vital for the survival of a species , and sexual reproduction helps maintain this diversity. But what happens when a species doesn’t reproduce sexually? Usually, it’s a recipe for low genetic diversity and a ticket to extinction. Yet, in the realm of clonal raider ants, this doesn’t seem to be the case. Why so? Genetic diversity of clonal raider ants To give you some context, the clonal raider ant is a blind, queenless creature found in tropical settings around the globe. The species is originally native to Bangladesh and reproduces through parthenogenesis. This type of asexual reproduction results in offspring that inherit two sets of genetically identical chromosomes from the mother – in other words, clone daughters. Now, you’d be forgiven for thinking that this should lead to a drastic loss in genetic diversity and, over time, species collapse . But these resilient little creatu...
Post a Comment
Read more