The role of microRNAs in understanding sex-based differences in Alzheimer's disease.
Alzheimer’s disease
Biomarkers
Meta-analysis
MicroRNAs
Sex-based differences
Systematic review
Transcriptomics
Journal
Biology of sex differences
ISSN: 2042-6410
Titre abrégé: Biol Sex Differ
Pays: England
ID NLM: 101548963
Informations de publication
Date de publication:
31 Jan 2024
31 Jan 2024
Historique:
received:
02
10
2023
accepted:
23
01
2024
medline:
1
2
2024
pubmed:
1
2
2024
entrez:
31
1
2024
Statut:
epublish
Résumé
The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment. A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms. Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process. Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information. Alzheimer's disease (AD)—a neurodegenerative disease mainly affecting older patients—is characterized by cognitive deterioration, memory loss, and progressive incapacitation in daily activities. While AD affects almost twice as many females as males, and cognitive deterioration and brain atrophy develop more rapidly in females, the biological causes of these differences remain poorly understood. MicroRNAs (miRNAs) regulate gene expression and impact a wide variety of biological processes; therefore, studying the differential expression of miRNAs in female and male AD patients could contribute to a better understanding of the disease. We reviewed studies of miRNA expression in female and male AD patients and integrated results using a meta-analysis methodology and then identified those genes regulated by the altered miRNAs to establish an association with biological processes. We found 16 (females) and 22 (males) miRNAs altered in the blood of AD patients. Functional enrichment revealed sex-based differences in the affected altered biological processes—protein modification and degradation and cell death in male AD patients and RNA processing in female AD patients. A similar analysis in the brains of AD patients revealed six (females) and four (males) miRNAs with altered expression; however, our analysis failed to highlight any specifically altered biological processes. Overall, we highlight the sex-based differential expression of miRNAs (and biological processes affected) in the blood and brain of AD patients.
Sections du résumé
BACKGROUND
BACKGROUND
The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment.
METHODS
METHODS
A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms.
RESULTS
RESULTS
Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process.
CONCLUSIONS
CONCLUSIONS
Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.
Alzheimer's disease (AD)—a neurodegenerative disease mainly affecting older patients—is characterized by cognitive deterioration, memory loss, and progressive incapacitation in daily activities. While AD affects almost twice as many females as males, and cognitive deterioration and brain atrophy develop more rapidly in females, the biological causes of these differences remain poorly understood. MicroRNAs (miRNAs) regulate gene expression and impact a wide variety of biological processes; therefore, studying the differential expression of miRNAs in female and male AD patients could contribute to a better understanding of the disease. We reviewed studies of miRNA expression in female and male AD patients and integrated results using a meta-analysis methodology and then identified those genes regulated by the altered miRNAs to establish an association with biological processes. We found 16 (females) and 22 (males) miRNAs altered in the blood of AD patients. Functional enrichment revealed sex-based differences in the affected altered biological processes—protein modification and degradation and cell death in male AD patients and RNA processing in female AD patients. A similar analysis in the brains of AD patients revealed six (females) and four (males) miRNAs with altered expression; however, our analysis failed to highlight any specifically altered biological processes. Overall, we highlight the sex-based differential expression of miRNAs (and biological processes affected) in the blood and brain of AD patients.
Autres résumés
Type: plain-language-summary
(eng)
Alzheimer's disease (AD)—a neurodegenerative disease mainly affecting older patients—is characterized by cognitive deterioration, memory loss, and progressive incapacitation in daily activities. While AD affects almost twice as many females as males, and cognitive deterioration and brain atrophy develop more rapidly in females, the biological causes of these differences remain poorly understood. MicroRNAs (miRNAs) regulate gene expression and impact a wide variety of biological processes; therefore, studying the differential expression of miRNAs in female and male AD patients could contribute to a better understanding of the disease. We reviewed studies of miRNA expression in female and male AD patients and integrated results using a meta-analysis methodology and then identified those genes regulated by the altered miRNAs to establish an association with biological processes. We found 16 (females) and 22 (males) miRNAs altered in the blood of AD patients. Functional enrichment revealed sex-based differences in the affected altered biological processes—protein modification and degradation and cell death in male AD patients and RNA processing in female AD patients. A similar analysis in the brains of AD patients revealed six (females) and four (males) miRNAs with altered expression; however, our analysis failed to highlight any specifically altered biological processes. Overall, we highlight the sex-based differential expression of miRNAs (and biological processes affected) in the blood and brain of AD patients.
Identifiants
pubmed: 38297404
doi: 10.1186/s13293-024-00588-1
pii: 10.1186/s13293-024-00588-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
13Subventions
Organisme : Instituto de Salud Carlos III
ID : IMP/00019
Organisme : Ministerio de Ciencia e Innovación
ID : PID2021-124430OA-I00
Organisme : Universitat de València
ID : MS21-074
Informations de copyright
© 2024. The Author(s).
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