Differential Transcriptional Programs Reveal Modular Network Rearrangements Associated with Late-Onset Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2361 - 2361

Published: March 6, 2025

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 progression. Network-based approaches offer way to assess phenotype-specific states. In this study, we calculated key network metrics characterize the transcriptional structure organization in LOAD, focusing on genes implicated pathology within dorsolateral prefrontal cortex (DLPFC). Our findings revealed disease-specific coexpression markers metabolic functions. Additionally, significant differences were observed at both mesoscopic local levels control networks, along restructuring of gene functions into distinct modules. These results show molecular reorganization program occurring highlighting specific adaptations that may contribute or cellular responses pathological stressors. support development unified model for causal mechanisms AD, suggesting its manifestations arise working together produce disease’s complex clinical patho-phenotype.

Language: Английский

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Gastrodin Alleviates Tau Pathology by Targeting the Alzheimer's Risk Gene FERMT2, Reversing the Reduction in Brain Viscoelasticity

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: March 1, 2025

The pathogenesis of Alzheimer's disease (AD) remains incompletely elucidated, and there is a notable deficiency in effective safe therapeutic interventions. influence brain matrix viscoelasticity on the progression AD has frequently been underestimated. It imperative to elucidate these overlooked pathogenic factors innovate novel strategies for AD. Gastrodin, bioactive constituent derived from traditional Chinese medicinal herb Gastrodia elata, exhibits range pharmacological properties, notably enhancement neural function. Nevertheless, underlying mechanisms its action remain insufficiently elucidated. Consequently, this study seeks examine effects gastrodin context AD, with particular emphasis potential viscoelastic properties matrix. This employs methodologies, including Morris water maze test, Y-maze spontaneous alternation atomic force microscopy (AFM), immunofluorescence, transmission electron microscopy, molecular docking, Cellular Thermal Shift Assay (CETSA), demonstrate that mitigates tau pathology by modulating FERMT2, thereby reversing deterioration mechanical brain. Gastrodin administration via gavage demonstrated mitigate cognitive decline associated attenuate hyperphosphorylation protein hippocampus cortex, ameliorate synaptic damage. Additionally, was observed counteract reduction 3xTg-AD mice, as evidenced upregulation extracellular components pertinent viscoelasticity, collagen types I IV. Furthermore, docking CETSA revealed strong binding affinity between FERMT2. treatment resulted FERMT2 fluorescence intensity, which selectively expressed astrocytes. contributed restoration blood-brain barrier (BBB) modulated expression levels inflammatory mediators interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), metallopeptidase 8 (MMP8). pathology, enhancing learning memory mouse models. effect may be mediated through modulation cerebral mechanosensor facilitates structure process potentially linked maintenance BBB integrity factor release.

Language: Английский

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Is the Relationship Between Cardiovascular Disease and Alzheimer’s Disease Genetic? A Scoping Review

Genes, Journal Year: 2024, Volume and Issue: 15(12), P. 1509 - 1509

Published: Nov. 25, 2024

Cardiovascular disease (CVD) and Alzheimer's (AD) are two diseases highly prevalent in the aging population often co-occur. The exact relationship between is uncertain, though epidemiological studies have demonstrated that CVDs appear to increase risk of AD vice versa. This scoping review aims examine current identified overlapping genetics at individual gene level shared pathway level. Following PRISMA-ScR guidelines for a review, we searched PubMed Scopus databases from 1990 October 2024 articles involved (1) CVDs, (2) AD, (3) used statistical methods parse genetic relationships. Our search yielded 2918 articles, which 274 passed screening were organized into main sections: evidence risk; mechanisms. genes Highly penetrant familial simultaneously AD. However, most cases, sets dysregulated within larger-scale mechanisms, like changes lipid metabolism, blood pressure regulation, BBB breakdown, both contribute progression.

Language: Английский

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