Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2019-08, Vol.28 (8), p.2111-2123.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •Increased glial classical complement expression in amyloidosis and tauopathy models•C3 deficiency rescues plaque-proximal synapse loss in PS2APP mice•C3 deficiency mitigates neurodegeneration and neuronal loss in TauP301S mice•C3 protein is increased in brains and cerebrospinal fluid from AD patients Wu et al. show that loss of the central complement component C3, which is elevated and activated in brains and cerebrospinal fluid from AD patients, ameliorates synapse loss and neurodegeneration in amyloidosis and tauopathy AD mouse models despite ongoing glial activation.