{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:50:28Z","timestamp":1791859828402,"version":"4.3.4"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Verein zur F\u00f6rderung von Wissenschaft und Forschung an der Medizinischen Fakult\u00e4t der LMU M\u00fcnchen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Synaptic loss is an early hallmark of Alzheimer\u2019s disease (AD), predominantly driven by aberrant microglial reactivity. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-\u03b3) agonist with anti-diabetic properties, has been shown to suppress microglial activity and improve cognitive performance in both AD models and clinical studies. However, whether its neuroprotective effects involve direct modulation of synaptic architecture remains unclear.<\/jats:p>\n                  <jats:p>Here, using longitudinal in vivo two-photon imaging, multi-channel immunohistochemistry, super-resolution confocal microscopy and three-dimensional reconstruction techniques in an AD mouse model, we analyse synaptic and microglial interactions.<\/jats:p>\n                  <jats:p>We show that a 4-week pioglitazone treatment preserves dendritic spine density and enhances spine stability over time. Mechanistically, pioglitazone reduces synaptic C1q deposition, thereby limiting complement-mediated microglial synaptic engulfment and attenuating synapse loss.<\/jats:p>\n                  <jats:p>These findings identify pioglitazone as a modulator of complement-dependent microglial synaptic pruning and support its therapeutic potential in preserving synaptic integrity during early AD pathogenesis.<\/jats:p>","DOI":"10.1093\/brain\/awaf462","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:05:54Z","timestamp":1765544754000},"page":"668-679","source":"Crossref","is-referenced-by-count":9,"title":["Pioglitazone attenuates complement-mediated microglial synaptic engulfment in an Alzheimer\u2019s disease model"],"prefix":"10.1093","volume":"149","author":[{"given":"Juan","family":"Zu","sequence":"first","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]},{"name":"Munich Medical Research School, Ludwig Maximilian University of Munich , Munich 80331 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Li","sequence":"additional","affiliation":[{"name":"Munich Medical Research School, Ludwig Maximilian University of Munich , Munich 80331 ,","place":["Germany"]},{"name":"Department of Medicine IV, University Hospital, Ludwig Maximilian University of Munich , Munich 80331 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-9045","authenticated-orcid":false,"given":"Mochen","family":"Cui","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]},{"name":"Munich Medical Research School, Ludwig Maximilian University of Munich , Munich 80331 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2655-1365","authenticated-orcid":false,"given":"Xinwu","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8534-0875","authenticated-orcid":false,"given":"Zhouyang","family":"Pan","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1552-6243","authenticated-orcid":false,"given":"Xiaohe","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Gentz","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerda","family":"Mitteregger-Kretzschmar","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Herms","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]},{"name":"Munich Cluster for Systems Neurology (SyNergy) , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6135-1830","authenticated-orcid":false,"given":"Yuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"2026020710022008800_awaf462-B1","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1176\/ajp.151.8.1105","article-title":"Inflammatory mechanisms in Alzheimer\u2019s disease: Implications for therapy","volume":"151","author":"Aisen","year":"1994","journal-title":"Am J Psychiatry"},{"key":"2026020710022008800_awaf462-B2","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0197-4580(00)00124-X","article-title":"Inflammation and Alzheimer\u2019s disease","volume":"21","author":"Akiyama","year":"2000","journal-title":"Neurobiol 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