Complement C3 Is Activated in Human AD Brain and Is Required for Neurodegeneration in Mouse Models of Amyloidosis and Tauopathy - PubMed (original) (raw)

. 2019 Aug 20;28(8):2111-2123.e6.

doi: 10.1016/j.celrep.2019.07.060.

Borislav Dejanovic 1, Vineela D Gandham 2, Alvin Gogineni 2, Rose Edmonds 3, Stephen Schauer 3, Karpagam Srinivasan 1, Melanie A Huntley 4, Yuanyuan Wang 1, Tzu-Ming Wang 1, Maj Hedehus 2, Kai H Barck 2, Maya Stark 5, Hai Ngu 5, Oded Foreman 5, William J Meilandt 1, Justin Elstrott 2, Michael C Chang 3, David V Hansen 1, Richard A D Carano 2, Morgan Sheng 1, Jesse E Hanson 6

Affiliations

• PMID: 31433986
• DOI: 10.1016/j.celrep.2019.07.060

Free article

Complement C3 Is Activated in Human AD Brain and Is Required for Neurodegeneration in Mouse Models of Amyloidosis and Tauopathy

Tiffany Wu et al. Cell Rep. 2019.

Free article

Abstract

Complement pathway overactivation can lead to neuronal damage in various neurological diseases. Although Alzheimer's disease (AD) is characterized by β-amyloid plaques and tau tangles, previous work examining complement has largely focused on amyloidosis models. We find that glial cells show increased expression of classical complement components and the central component C3 in mouse models of amyloidosis (PS2APP) and more extensively tauopathy (TauP301S). Blocking complement function by deleting C3 rescues plaque-associated synapse loss in PS2APP mice and ameliorates neuron loss and brain atrophy in TauP301S mice, improving neurophysiological and behavioral measurements. In addition, C3 protein is elevated in AD patient brains, including at synapses, and levels and processing of C3 are increased in AD patient CSF and correlate with tau. These results demonstrate that complement activation contributes to neurodegeneration caused by tau pathology and suggest that blocking C3 function might be protective in AD and other tauopathies.

Keywords: Alzheimer’s disease; C3; amyloidosis; astrocyte; complement; microglia; neurodegeneration; neuroinflammation; synapse; tauopathy.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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