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@ARTICLE{Zu:285042,
      author       = {Zu, Juan and Li, Cong and Cui, Mochen and Liu, Xinwu and
                      Pan, Zhouyang and Li, Xiaohe and Zhang, Fang and Gentz,
                      Johanna and Mitteregger-Kretzschmar, Gerda and Herms, Jochen
                      and Shi, Yuan},
      title        = {{P}ioglitazone attenuates complement-mediated microglial
                      synaptic engulfment in an {A}lzheimer's disease model.},
      journal      = {Brain},
      volume       = {149},
      number       = {2},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2026-00166},
      pages        = {668 - 679},
      year         = {2026},
      abstract     = {Synaptic loss is an early hallmark of Alzheimer's disease
                      (AD), predominantly driven by aberrant microglial
                      reactivity. Pioglitazone, a peroxisome
                      proliferator-activated receptor gamma (PPAR-γ) 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. 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. 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. 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.},
      keywords     = {Pioglitazone: pharmacology / Animals / Alzheimer Disease:
                      drug therapy / Alzheimer Disease: pathology / Alzheimer
                      Disease: metabolism / Microglia: drug effects / Microglia:
                      metabolism / Microglia: pathology / Mice / Synapses: drug
                      effects / Synapses: pathology / Disease Models, Animal /
                      Mice, Transgenic / Dendritic Spines: drug effects /
                      Dendritic Spines: pathology / Complement C1q: metabolism /
                      Mice, Inbred C57BL / Male / PPAR gamma: agonists / Humans /
                      Alzheimer’s disease (Other) / microglia (Other) /
                      peroxisome proliferator-activated receptor-γ (Other) /
                      pioglitazone (Other) / synaptic plasticity (Other) /
                      Pioglitazone (NLM Chemicals) / Complement C1q (NLM
                      Chemicals) / PPAR gamma (NLM Chemicals)},
      cin          = {AG Herms},
      ddc          = {610},
      cid          = {I:(DE-2719)1110001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41396874},
      doi          = {10.1093/brain/awaf462},
      url          = {https://pub.dzne.de/record/285042},
}