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Complement C3 Is Activated in Human AD Brain and Is Required for Neurodegeneration in Mouse Models of Amyloidosis and Tauopathy
Name
1-s2.0-S2211124719309647-main.pdf
Description
Published version
Size
5.7 MB
Format
Adobe PDF
Checksum (MD5)
9b0b28d69a011cca5b9d93dcb4d784aa
Author(s)
Wu, Tiffany
Dejanovic, Borislav
Gandham, Vineela D
Gogineni, Alvin
Edmonds, Rose
Schauer, Stephen
Srinivasan, Karpagam
Huntley, Melanie A
Wang, Yuanyuan
Wang, Tzu-Ming
Date Issued
2019
Journal
Cell Reports
Publisher
Elsevier BV
Version
Final published version
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.
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
10.1016/J.CELREP.2019.07.060
