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We characterized glial fibrillary acidic protein(GFAP) and purinergic P2X7 receptor(P2X7R) alterations in AD and their associations with amyloid-\u03b2 levels, tau pathology and synaptic density. Immunostaining(P2X7R, GFAP, amyloid-\u03b2, and phospho-tau) and autoradiography using [\n                    <jats:sup>18<\/jats:sup>\n                    F]JNJ-64413739 for P2X7R were performed in postmortem hippocampal and entorhinal cortex tissues from 42 AD patients and 35 nondemented-controls. Compared with nondemented-controls, AD hippocampi and the entorhinal cortex presented reactive astrocytes with increased GFAP and P2X7R levels. GFAP and P2X7R levels were positively correlated with amyloid-\u03b2, CERAD score, phospho-tau, and Braak stage and enriched around cored plaques. In conclusion, we found increased levels of GFAP and P2X7R in hippocampal and entorhinal cortex of AD patients compared with controls, associated with amyloid-\u03b2, tau, and Braak stage, highlighting the importance of astrogliosis in AD.\n                  <\/jats:p>","DOI":"10.1186\/s13195-025-01916-2","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T08:03:49Z","timestamp":1764057829000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Increased levels of GFAP and purinergic P2X7 receptor in Alzheimer\u2019s disease brain are associated with A\u03b2, tau pathologies and synaptic loss"],"prefix":"10.1186","volume":"17","author":[{"given":"Cinzia A.","family":"Maschio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upasana","family":"Maheshwari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Konietzko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Razansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Nordberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Rominger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Llop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger M.","family":"Nitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"5","key":"1916_CR1","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","volume":"25","author":"MT Heneka","year":"2025","unstructured":"Heneka MT, van der Flier WM, Jessen F, Hoozemanns J, Thal DR, Boche D, et al. 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Mol Psychiatry. 2025;30(4):1430\u20139. https:\/\/doi.org\/10.1038\/s41380-024-02753-9.","journal-title":"Mol Psychiatry"}],"container-title":["Alzheimer's Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-025-01916-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13195-025-01916-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-025-01916-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T13:54:19Z","timestamp":1781618059000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13195-025-01916-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1916"],"URL":"https:\/\/doi.org\/10.1186\/s13195-025-01916-2","relation":{},"ISSN":["1758-9193"],"issn-type":[{"value":"1758-9193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]},"assertion":[{"value":"30 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Part of the manuscript is shared as preprint on Biorxiv\n                      \n                      .","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted according to the principles of the Declaration of Helsinki and subsequent revisions. All the autopsied human brain tissue experiments were carried out in accordance with ethical permission obtained from the regional human ethics committee and the medical ethics committee of the VU Medical Center for NBB tissue.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All materials were collected from donors or from whom written informed consent was obtained for a brain autopsy, and the use of the materials and clinical information for research purposes were obtained by the NBB. The study was conducted according to the principles of the Declaration of Helsinki and subsequent revisions. All the autopsied human brain tissue experiments were carried out in accordance with ethical permission obtained from the regional human ethics committee and the medical ethics committee of the VU Medical Center for NBB tissue.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RMN and CH are employees and shareholder of Neurimmune AG. The other authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"274"}}