Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humans
Abstract Analysis of system-wide cellular communication changes in Alzheimer’s disease (AD) has recently been enabled by single nucleus RNA sequencing (snRNA-seq) and new computational methods. Here, we combined these to analyze data from postmortem human tissue from the entorhinal cortex of people...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-10795-4 |
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| author | Katrina Bartas Megan Nguyen Wei Zhao May Hui Qing Nie Kevin T. Beier |
| author_facet | Katrina Bartas Megan Nguyen Wei Zhao May Hui Qing Nie Kevin T. Beier |
| author_sort | Katrina Bartas |
| collection | DOAJ |
| description | Abstract Analysis of system-wide cellular communication changes in Alzheimer’s disease (AD) has recently been enabled by single nucleus RNA sequencing (snRNA-seq) and new computational methods. Here, we combined these to analyze data from postmortem human tissue from the entorhinal cortex of people with AD and compared our findings to those from multiomic data from the 5xFAD amyloidogenic mouse model at two different time points. Using the cellular communication inference tool CellChat we found that disease-related changes were largely related to neuronal excitability as well as synaptic communication, with specific signaling pathways including BMP, EGF, and EPHA, and relatively poor conservation of glial-related changes during disease. Further analysis using the neuron-specific NeuronChat revealed changes relating to metabotropic glutamate receptors as well as neuronal adhesion molecules including neurexins and neuroligins. Our results that cellular processes relating to excitotoxicity are the best conserved between 5xFAD mice and AD suggest that excitotoxicity is the main common feature between pathogenesis in 5xFAD mice and people with AD. |
| format | Article |
| id | doaj-art-5f7d28de85da434fac954f2dbb076d56 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5f7d28de85da434fac954f2dbb076d562025-08-20T03:45:57ZengNature PortfolioScientific Reports2045-23222025-07-0115112210.1038/s41598-025-10795-4Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humansKatrina Bartas0Megan Nguyen1Wei Zhao2May Hui3Qing Nie4Kevin T. Beier5Program in Mathematical, Computational, and Systems Biology, University of California, IrvineDepartment of Physiology and Biophysics, University of California, IrvineDepartment of Mathematics, NSF-Simons Center for Multiscale Cell Fate Research, University of California, IrvineDepartment of Physiology and Biophysics, University of California, IrvineDepartment of Mathematics, NSF-Simons Center for Multiscale Cell Fate Research, University of California, IrvineDepartment of Physiology and Biophysics, University of California, IrvineAbstract Analysis of system-wide cellular communication changes in Alzheimer’s disease (AD) has recently been enabled by single nucleus RNA sequencing (snRNA-seq) and new computational methods. Here, we combined these to analyze data from postmortem human tissue from the entorhinal cortex of people with AD and compared our findings to those from multiomic data from the 5xFAD amyloidogenic mouse model at two different time points. Using the cellular communication inference tool CellChat we found that disease-related changes were largely related to neuronal excitability as well as synaptic communication, with specific signaling pathways including BMP, EGF, and EPHA, and relatively poor conservation of glial-related changes during disease. Further analysis using the neuron-specific NeuronChat revealed changes relating to metabotropic glutamate receptors as well as neuronal adhesion molecules including neurexins and neuroligins. Our results that cellular processes relating to excitotoxicity are the best conserved between 5xFAD mice and AD suggest that excitotoxicity is the main common feature between pathogenesis in 5xFAD mice and people with AD.https://doi.org/10.1038/s41598-025-10795-4 |
| spellingShingle | Katrina Bartas Megan Nguyen Wei Zhao May Hui Qing Nie Kevin T. Beier Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humans Scientific Reports |
| title | Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humans |
| title_full | Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humans |
| title_fullStr | Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humans |
| title_full_unstemmed | Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humans |
| title_short | Analysis of changes in intercellular communications in Alzheimer’s disease reveals conserved changes in glutamatergic transmission in mice and humans |
| title_sort | analysis of changes in intercellular communications in alzheimer s disease reveals conserved changes in glutamatergic transmission in mice and humans |
| url | https://doi.org/10.1038/s41598-025-10795-4 |
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