Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer’s disease mouse models

Borislav Dejanovic, Tiffany Wu, Ming‐Chi Tsai, David Graykowski, Vineela Gandham, Christopher M. Rose, Corey E. Bakalarski, Hai Ngu, Yuanyuan Wang, Shristi Pandey, Mitchell G. Rezzonico, Brad A. Friedman, Rose Edmonds, Ann De Mazière, Raphael Rakosi-Schmidt, Tarjinder Singh, Judith Klumperman, Oded Foreman, Michael Chang, Luke Xie, Morgan Sheng, Jesse E. Hanson

Nature Aging · 2022

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Summary

Microglia and complement can mediate neurodegeneration in Alzheimer's disease (AD). By integrative multi-omics analysis, here we show that astrocytic and microglial proteins are increased in Tau<sup>P301S</sup> synapse fractions with age and in a C1q-dependent manner. In addition to microglia, we identified that astrocytes contribute substantially to synapse elimination in Tau<sup>P301S</sup> hippocampi. Notably, we found relatively more excitatory synapse marker proteins in astrocytic lysosomes, whereas microglial lysosomes contained more inhibitory synapse material. C1q deletion reduced astrocyte-synapse association and decreased astrocytic and microglial synapses engulfment in Tau<sup>P301S</sup> mice and rescued synapse density. Finally, in an AD mouse model that combines β-amyloid and

Source type
Peer-reviewed study
DOI
10.1038/s43587-022-00281-1
Catalogue ID
SNmois81sf-4xgl58
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