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Senescence-related genes and proteins in the development of Alzheimer's disease: evidence from transcriptomic and Mendelian randomization analysis.
- Source :
- Frontiers in Aging Neuroscience; 2024, p1-10, 10p
- Publication Year :
- 2024
-
Abstract
- Purpose: Alzheimer's disease (AD) is a common neurodegenerative disease, which can lead to cognitive impairment and dementia. Since AD is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between senescence-related genes and proteins (SRGs and SRPs) and the development of AD. Design: The whole study was based on transcriptomic analysis of control and AD brain tissues and Mendelian randomization (MR) analysis. Methods: For transcriptomic analysis, GSE5281 dataset from GEO database contains the transcriptomic data of human brain tissues (n = 161) from control group and AD patients. The expression of SRGs in control and AD brain tissues were compared by Student's t test. For MR analysis, the instrumental singlenucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome. The causality between plasma levels of SRPs and AD was explored using GWAS data of AD from Lambert et al. (17,008 cases and 37,154 controls) and further validated by using data from FinnGen consortium (6,489 patients and 170,489 controls). MR estimate was performed using the inversevariance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested. Results: Transcriptomic analysis identified 36 up-regulated (including PLAUR) and 8 down-regulated SRGs in AD brain tissues. In addition, the MR results at both discovery and validation stages supported the causality between plasma levels of PLAUR (IVW-p = 3.04E-2, odds ratio [OR]= 1.15), CD55 (IVW-p = 1.56E-3, OR= 0.86), and SERPINE2 (IVW-p = 2.74E-2, OR= 0.91) and the risk of AD. Conclusion: Our findings identified that PLAUR, as an SRG, may take part in the development of AD and found that high plasma levels of PLAUR was associated with increased risk of AD, indicating that this gene was a risk factor for this disease and providing the rationale of existing drugs or new preventative and therapeutic strategies. [ABSTRACT FROM AUTHOR]
- Subjects :
- ALZHEIMER'S disease risk factors
GENETICS of Alzheimer's disease
BRAIN anatomy
RISK assessment
T-test (Statistics)
GENOME-wide association studies
GENOMICS
CELLULAR aging
BLOOD proteins
GENETIC markers
DESCRIPTIVE statistics
GENE mapping
TRANSCRIPTION factors
GENETIC polymorphisms
ODDS ratio
GENE expression profiling
COGNITION disorders
PROTEOMICS
DEMENTIA
DATA analysis software
CONFIDENCE intervals
SINGLE nucleotide polymorphisms
SEQUENCE analysis
Subjects
Details
- Language :
- English
- ISSN :
- 16634365
- Database :
- Complementary Index
- Journal :
- Frontiers in Aging Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 179079873
- Full Text :
- https://doi.org/10.3389/fnagi.2024.1423725