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Peer-reviewedCC BYScience

C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain

  • Gerard Crowley1,2
  • Minjung Kim1,2
  • Nathanael O’Neill3,2
  • Emir Turkes1,2
  • Fateme Ghasemi4,5
  • Luca Giudice4,2
  • Sebastiaan De Schepper1,2
  • Benjy J.Y. Tan6,7,2
  • Benito Maffei3,2
  • Laís S. S. Ferreira1,2
  • Julie Rebejac1,2
  • Javier Rueda‐Carrasco1,5
21 more authors
  • Margarita Toneva1,5
  • John Christian Fajardo1,8
  • Judy Z. Ge1,2
  • Zhengyue Grace Yang1,2
  • Paula Korhonen4,2
  • Phillip Muckett1,2
  • Damaris Bennett9,5
  • Camille Paoletti1,2
  • Tammie Tao Min Sow7
  • David A Posner6,7
  • Annerieke S. R. Sierksma10,11
  • Dimitra Sokolova1
  • Viktoras Konstantellos1
  • Leen Ali12,13
  • Kiavash Movahedi12
  • Andrew F. MacAskill14
  • Victor L. J. Tybulewicz9
  • Tarja Malm4
  • Gabriele Lignani3
  • Menna Ruth Clatworthy6,15,7
  • Soyon Youngae Hong1
15 affiliations
  1. 1UK Dementia Research Institute, Institute of Neurology, University College London, London, UK
  2. 2University College London
  3. 3Research Department of Epilepsy, Queen Square Institute of Neurology, University College London, London, UK
  4. 4A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
  5. 5University of Cambridge
  6. 6Cambridge Institute of Therapeutic Immunology and Infectious Diseases, University of Cambridge, Cambridge, UK
  7. 7Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
  8. 8Katholieke Universiteit Leuven
  9. 9The Francis Crick Institute, London, UK
  10. 10Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute, Katholieke Universiteit Leuven, Leuven, Belgium
  11. 11VIB-KU Leuven Center for Neuroscience, Leuven, Belgium
  12. 12Brain and Systems Immunology Laboratory, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium
  13. 13Laboratory of Myeloid Cell Immunology, VIB Center for Inflammation Research, Brussels, Belgium
  14. 14Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
  15. 15Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
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Abstract

Complement component 1q (C1q), the initiator of the classical complement cascade, mediates synaptic elimination in development and disease, yet the triggers for its deposition on synapses remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity induces region-specific, C1q-dependent synapse loss in the adult hippocampus. Suppressing perforant pathway hyperactivity in a mouse model of Alzheimer's disease reduced local amyloid-β amounts and C1q deposition and partially rescued synapse loss. Combining spatial transcriptomics, live cell tracking, and super-resolution microscopy, we identified association of antibody-secreting B-lineage cells in the adult hippocampus with activity-dependent, C1q-mediated synapse loss under physiological conditions. Together, these findings link neuronal hyperactivity to C1q-mediated synapse loss in the adult brain and implicate immunoglobulins as players in this process.

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Cite

BibTeXRIS
BibTeX
@article{crowley2026immunoglobulins,
  title = {{C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain}},
  author = {Gerard Crowley and Minjung Kim and Nathanael O’Neill and Emir Turkes and Fateme Ghasemi and Luca Giudice and Sebastiaan De Schepper and Benjy J.Y. Tan and Benito Maffei and Laís S. S. Ferreira and Julie Rebejac and Javier Rueda‐Carrasco and Margarita Toneva and John Christian Fajardo and Judy Z. Ge and Zhengyue Grace Yang and Paula Korhonen and Phillip Muckett and Damaris Bennett and Camille Paoletti and Tammie Tao Min Sow and David A Posner and Annerieke S. R. Sierksma and Dimitra Sokolova and Viktoras Konstantellos and Leen Ali and Kiavash Movahedi and Andrew F. MacAskill and Victor L. J. Tybulewicz and Tarja Malm and Gabriele Lignani and Menna Ruth Clatworthy and Soyon Youngae Hong},
  journal = {Science},
  year = {2026},
  month = jul,
  doi = {10.1126/science.adv1219},
  url = {https://doi.org/10.1126/science.adv1219},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain
AU  - Gerard Crowley
AU  - Minjung Kim
AU  - Nathanael O’Neill
AU  - Emir Turkes
AU  - Fateme Ghasemi
AU  - Luca Giudice
AU  - Sebastiaan De Schepper
AU  - Benjy J.Y. Tan
AU  - Benito Maffei
AU  - Laís S. S. Ferreira
AU  - Julie Rebejac
AU  - Javier Rueda‐Carrasco
AU  - Margarita Toneva
AU  - John Christian Fajardo
AU  - Judy Z. Ge
AU  - Zhengyue Grace Yang
AU  - Paula Korhonen
AU  - Phillip Muckett
AU  - Damaris Bennett
AU  - Camille Paoletti
AU  - Tammie Tao Min Sow
AU  - David A Posner
AU  - Annerieke S. R. Sierksma
AU  - Dimitra Sokolova
AU  - Viktoras Konstantellos
AU  - Leen Ali
AU  - Kiavash Movahedi
AU  - Andrew F. MacAskill
AU  - Victor L. J. Tybulewicz
AU  - Tarja Malm
AU  - Gabriele Lignani
AU  - Menna Ruth Clatworthy
AU  - Soyon Youngae Hong
PY  - 2026
DA  - 2026/07/09
JO  - Science
DO  - 10.1126/science.adv1219
UR  - https://doi.org/10.1126/science.adv1219
AB  - Complement component 1q (C1q), the initiator of the classical complement cascade, mediates synaptic elimination in development and disease, yet the triggers for its deposition on synapses remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity induces region-specific, C1q-dependent synapse loss in the adult hippocampus. Suppressing perforant pathway hyperactivity in a mouse model of Alzheimer's disease reduced local amyloid-β amounts and C1q deposition and partially rescued synapse loss. Combining spatial transcriptomics, live cell tracking, and super-resolution microscopy, we identified association of antibody-secreting B-lineage cells in the adult hippocampus with activity-dependent, C1q-mediated synapse loss under physiological conditions. Together, these findings link neuronal hyperactivity to C1q-mediated synapse loss in the adult brain and implicate immunoglobulins as players in this process.
SN  - 0036-8075
SN  - 0193-4511
SN  - 1095-9203
ER  -