Zatcepin, Artem and Gnoerich, Johannes and Rauchmann, Boris-Stephan and Bartos, Laura M. and Wagner, Stephan and Franzmeier, Nicolai and Malpetti, Maura and Xiang, Xianyuan and Shi, Yuan and Parhizkar, Samira and Grosch, Maximilian and Wind-Mark, Karin and Kunte, Sebastian T. and Beyer, Leonie and Meyer, Carolin and Broesamle, Desiree and Wendeln, Ann-Christin and Osei-Sarpong, Collins and Heindl, Steffanie and Liesz, Arthur and Stoecklein, Sophia and Biechele, Gloria and Finze, Anika and Eckenweber, Florian and Lindner, Simon and Rominger, Axel and Bartenstein, Peter and Willem, Michael and Tahirovic, Sabina and Herms, Jochen and Buerger, Katharina and Simons, Mikael and Haass, Christian and Rupprecht, Rainer and Riemenschneider, Markus J. and Albert, Nathalie L. and Beyer, Marc and Neher, Jonas J. and Paeger, Lars and Levin, Johannes and Hoeglinger, Guenter U. and Perneczky, Robert and Ziegler, Sibylle I. and Brendel, Matthias (2024) Regional desynchronization of microglial activity is associated with cognitive decline in Alzheimer's disease. MOLECULAR NEURODEGENERATION, 19 (1): 64. ISSN , 1750-1326
Full text not available from this repository. (Request a copy)Abstract
BackgroundMicroglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker.MethodsTo validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia and AD pathophysiology on TSPO-PET ICCs in the mouse brain, followed by translation to a human AD-continuum dataset. We correlated a personalized microglia desynchronization index with cognitive performance. Finally, we performed single-cell radiotracing (scRadiotracing) in mice to ensure the microglial source of the measured desynchronization.ResultsMicroglia-depleted mice showed a strong ICC reduction in all brain compartments, indicating microglia-specific desynchronization. AD mouse models demonstrated significant reductions of microglial synchronicity, associated with increasing variability of cellular radiotracer uptake in pathologically altered brain regions. Humans within the AD-continuum indicated a stage-depended reduction of microglia synchronicity associated with cognitive decline. scRadiotracing in mice showed that the increased TSPO signal was attributed to microglia.ConclusionUsing TSPO-PET imaging of mice with depleted microglia and scRadiotracing in an amyloid model, we provide first evidence that a microglia connectome can be assessed in the mouse brain. Microglia synchronicity is closely associated with cognitive decline in AD and could serve as an independent personalized biomarker for disease progression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATION; BRAIN; PET; EXPRESSION; Alzheimer's disease; Dementia; Microglia; Neuroinflammation; TSPO; PET; Brain connectivity; Microglia synchronicity; Microglia desynchronization |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Neuropathologie Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Jan 2026 12:21 |
| Last Modified: | 04 Feb 2026 08:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65452 |
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