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This study aimed to investigate meninges-hippocampus crosstalk and map the communication patterns during AD pathology development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed 5xFAD transgenic and PS19 tau-pathology mouse models and integrated bulk RNA sequencing, proteomics, and spatial transcriptomics across time-course analyses to distinguish AD pathology from normal aging processes. Transcription factor activity inference was coupled with ligand-receptor dynamics analysis to examine regulatory modules in homeostatic and disease-associated microglia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified structure-specific disease genes, including a robust 19-gene hippocampal signature that was reproducible across an independent 5xFAD dataset and PS19 tau-pathology dataset. Spatial analysis defined a disease progression axis that transferred to the independent spatial dataset, where meningeal spots were enriched in advanced disease progression layers and disease modules showed consistent gradients. Ligand-receptor and microglial-state LRaxis analyses further supported candidate communication axes associated with pathology gradients and state-specific regulatory modules in both homeostatic and disease-associated microglia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our spatial framework supports the meninges as a candidate modulatory interface associated with hippocampal pathology in AD mouse models. These mouse-derived, computationally inferred ligand-receptor and regulatory modules should be considered hypothesis-generating candidates that require validation in human AD tissues and functional perturbation studies before translational relevance can be inferred.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08414-5","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:25:05Z","timestamp":1782393905000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative transcriptomic analysis identifies meningeal-hippocampal immune communication in Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"24","author":[{"given":"Congcong","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhoushuai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"2","key":"8414_CR1","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","volume":"7","author":"GBDDF Collaborators","year":"2022","unstructured":"Collaborators GBDDF. 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