ArticleFrontiers in aging neuroscience2021
A Systematic Analysis on the Genes and Their Interaction Underlying the Comorbidity of Alzheimer's Disease and Major Depressive Disorder.
Article in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 13 citations in OpenAlex.
- Dihydroergotamine and Bromocriptine: Potential Drugs for the Treatment of Major Depressive Disorder and Alzheimer's Disease Comorbidity.Molecular neurobiology · 2025Article
- Multi-omics integration identifies NK cell dysregulation and a five-gene diagnostic signature in major depressive disorder.Frontiers in immunology · 2025Article
- Identification of novel biomarkers linking depressive disorder and Alzheimer's disease based on an integrative bioinformatics analysis.BMC genomic data · 2023Article
- Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism.Molecules (Basel, Switzerland) · 2022Review
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5 authors at 1 institution in 1 country.
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Abstract
backgroundDuring the past years, clinical and epidemiological studies have indicated a close relationship between Alzheimer's disease (AD) and other mental disorders like major depressive disorder (MDD). At the same time, a number of genes genetically associated with AD or MDD have been detected. However, our knowledge on the mechanisms that link the two disorders is still incomplete, and controversies exist. In such a situation, a systematic analysis on these genes could provide clues to understand the molecular features of two disorders and their comorbidity.
methodsIn this study, we compiled the genes reported to be associated with AD or MDD by a comprehensive search of human genetic studies and genes curated in disease-related database. Then, we investigated the features of the shared genes between AD and MDD using the functional enrichment analysis. Furthermore, the major biochemical pathways enriched in the AD- or MDD-associated genes were identified, and the cross talks between the pathways were analyzed. In addition, novel candidate genes related to AD and MDD were predicted in the context of human protein-protein interactome.
resultsWe obtained 650 AD-associated genes, 447 MDD-associated genes, and 77 shared genes between AD and MDD. The functional analysis revealed that biological processes involved in cognition, neural development, synaptic transmission, and immune-related processes were enriched in the common genes, indicating a complex mechanism underlying the comorbidity of the two diseases. In addition, we conducted the pathway enrichment analysis and found 102 shared pathways between AD and MDD, which involved in neuronal development, endocrine, cell growth, and immune response. By using the pathway cross-talk analysis, we found that these pathways could be roughly clustered into four modules, i.e., the immune response-related module, the neurodevelopmental module, the cancer or cell growth module, and the endocrine module. Furthermore, we obtained 37 novel candidate genes potentially related to AD and MDD with node degrees > 5.0 by mapping the shared genes to human protein-protein interaction network (PPIN). Finally, we found that 37 novel candidate genes are significantly expressed in the brain.
conclusionThese results indicated shared biological processes and pathways between AD and MDD and provided hints for the comorbidity of AD and MDD.
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