Differential Transcriptional Programs Reveal Modular Network Rearrangements Associated with Late-Onset Alzheimer’s Disease
Year: 2025
Type: article
Abstract: Alzheimer's disease (AD) is a complex, genetically heterogeneous disorder. The diverse phenotypes associated with AD result from interactions between genetic and environmental factors, influencing multiple biological pathways throughout disease progression. Network-based approaches offer a way to assess phenotype-specific states. In this study, we calculated key network metrics to characterize the network transcriptional structure and organization in LOAD, focusing on genes and pathways implicated in AD pathology within the dorsolateral prefrontal cortex (DLPFC). Our findings revealed disease-specific coexpression markers associated with diverse metabolic functions. Additionally, significant differences were observed at both the mesoscopic and local levels between AD and control networks, along with a restructuring of gene coexpression and biological functions into distinct transcriptional modules. These results show the molecular reorganization of the transcriptional program occurring in LOAD, highlighting specific adaptations that may contribute to or result from cellular responses to pathological stressors. Our findings may support the development of a unified model for the causal mechanisms of AD, suggesting that its diverse manifestations arise from multiple pathways working together to produce the disease's complex clinical patho-phenotype.
DOI: 10.3390/ijms26052361
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G1012872418, G1182502907, G1333920956, G133435157, G1561340194, G1624043100, G1641033535, Genetic Epidemiology of Cognitive Decline in an Aging Population Sample, G1751565318, G1837277402, G1874743943, G1919702628, G2054798532, G2291268058, G2336925225, G266544023, G2804083835, G2943483482, G3022843226, Exploring the Role of the Brain Transcriptome in Cognitive Decline, G3163301736, G3172397545, G3478357739, G3662117962, G3743240706, G3859312003, Pathway discovery, validation and compound identification for Alzheimer's disease, G4046709432, G4325974637, G4800707974, Risk Factors, Pathology, and Clinical Expressions of AD, G5018925220, G5070153293, G5216698141, Alzheimer's Disease Genetics Consortium, G5369702884, G541333419, G5456613342, G5713958695, G5774210394, G59208539, G6052603286, G6247109737, G6321218983, G6780642948, G6810051082, G7093142501, Discovery of Novel Proteomic Targets for Treatment of Alzheimer's Disease, G7315133172, G7479973302, G7583956497, G7911560998, G7964693420, G828200374, Deconstructing and modeling the single cell architecture of the Alzheimer brain, G896222438, G983864884
OpenAlex ID: W4408201724