Home > In process > Pioglitazone attenuates complement-mediated microglial synaptic engulfment in an Alzheimer's disease model. > print

001     285042
005     20260209102150.0
024 7 _ |a 10.1093/brain/awaf462
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024 7 _ |a 1460-2156
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037 _ _ |a DZNE-2026-00166
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Zu, Juan
|0 P:(DE-2719)9001924
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245 _ _ |a Pioglitazone attenuates complement-mediated microglial synaptic engulfment in an Alzheimer's disease model.
260 _ _ |a Oxford
|c 2026
|b Oxford Univ. Press
336 7 _ |a article
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520 _ _ |a 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.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a microglia
|2 Other
650 _ 7 |a peroxisome proliferator-activated receptor-γ
|2 Other
650 _ 7 |a pioglitazone
|2 Other
650 _ 7 |a synaptic plasticity
|2 Other
650 _ 7 |a Pioglitazone
|0 X4OV71U42S
|2 NLM Chemicals
650 _ 7 |a Complement C1q
|0 80295-33-6
|2 NLM Chemicals
650 _ 7 |a PPAR gamma
|2 NLM Chemicals
650 _ 2 |a Pioglitazone: pharmacology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Alzheimer Disease: drug therapy
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Microglia: drug effects
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Microglia: pathology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Synapses: drug effects
|2 MeSH
650 _ 2 |a Synapses: pathology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Dendritic Spines: drug effects
|2 MeSH
650 _ 2 |a Dendritic Spines: pathology
|2 MeSH
650 _ 2 |a Complement C1q: metabolism
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a PPAR gamma: agonists
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
700 1 _ |a Li, Cong
|b 1
700 1 _ |a Cui, Mochen
|0 P:(DE-2719)9002141
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700 1 _ |a Liu, Xinwu
|0 P:(DE-2719)9003588
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700 1 _ |a Pan, Zhouyang
|0 P:(DE-2719)9003796
|b 4
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700 1 _ |a Li, Xiaohe
|0 P:(DE-2719)9003834
|b 5
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700 1 _ |a Zhang, Fang
|0 P:(DE-2719)9001979
|b 6
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700 1 _ |a Gentz, Johanna
|0 P:(DE-2719)9002339
|b 7
|u dzne
700 1 _ |a Mitteregger-Kretzschmar, Gerda
|b 8
700 1 _ |a Herms, Jochen
|0 P:(DE-2719)2810441
|b 9
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700 1 _ |a Shi, Yuan
|0 P:(DE-2719)2811433
|b 10
|e Last author
773 _ _ |a 10.1093/brain/awaf462
|g Vol. 149, no. 2, p. 668 - 679
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|p 668 - 679
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