ArticleFrontiers in genetics2020
Phosphodiesterase 4D Gene Modifies the Functional Network of Patients With Mild Cognitive Impairment and Alzheimer's Disease.
Article in Frontiers in genetics, 2020. 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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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Deep joint learning diagnosis of Alzheimer's disease based on multimodal feature fusion.BioData mining · 2024Article
- Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.Aging and disease · 2024Article
- Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- The Repertoire of Small-Molecule PET Probes for Neuroinflammation Imaging: Challenges and Opportunities beyond TSPO.Journal of medicinal chemistry · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is affected by several genetic variants. It has been demonstrated that genetic variants affect brain organization and function. In this study, using whole genome-wide association studies (GWAS), we analyzed the functional magnetic resonance imaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative dataset (ADNI) dataset and identified genetic variants associated with the topology of the functional brain network http://www.adni-info.org. We found three novel loci (rs2409627, rs9647533, and rs11955845) in an intron of the phosphodiesterase 4D (PDE4D) gene that contribute to abnormalities in the topological organization of the functional network. In particular, compared to the wild-type genotype, the subjects carrying the PDE4D variants had altered network properties, including a significantly reduced clustering coefficient, small-worldness, global and local efficiency, a significantly enhanced path length and a normalized path length. In addition, we found that all global brain network attributes were affected by PDE4D variants to different extents as the disease progressed. Additionally, brain regions with alterations in nodal efficiency due to the variations in PDE4D were predominant in the limbic lobe, temporal lobe and frontal lobes. PDE4D has a great effect on memory consolidation and cognition through long-term potentiation (LTP) effects and/or the promotion of inflammatory effects. PDE4D variants might be a main reasons underlyling for the abnormal topological properties and cognitive impairment. Furthermore, we speculated that PDE4D is a risk factor for neural degenerative diseases and provided important clues for the earlier detection and therapeutic intervention for AD.
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