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Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model

alzheimers

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#1 Jim Morrison

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Posted 11 February 2019 - 07:27 PM


Not sure if fibrinogen has already been discussed in the context of AD. Maybe worth considering as an add-on to the dissolve & detoxify protocol by Turnbuckle. Old-school baby-aspirin may just do the job. The question is how to not overdo it and get into the zone were hemorrhagic strokes get an issue.

 

 

Published: February 5, 2019 DOI:https://doi.org/10.1...ron.2019.01.014
 
Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model

 

  • Fibrinogen is a blood-derived inducer of spine elimination
  • Fibrinogen promotes synapse loss in AD mice
  • 3D volume imaging of BBB disruption and Aβ in cleared human AD brain
  • Genetic inhibition of fibrinogen-CD11b binding improves cognition in AD mice
Summary
Cerebrovascular alterations are a key feature of Alzheimer’s disease (AD) pathogenesis. However, whether vascular damage contributes to synaptic dysfunction and how it synergizes with amyloid pathology to cause neuroinflammation and cognitive decline remain poorly understood. Here, we show that the blood protein fibrinogen induces spine elimination and promotes cognitive deficits mediated by CD11b-CD18 microglia activation. 3D molecular labeling in cleared mouse and human AD brains combined with repetitive in vivo two-photon imaging showed focal fibrinogen deposits associated with loss of dendritic spines independent of amyloid plaques. Fibrinogen-induced spine elimination was prevented by inhibiting reactive oxygen species (ROS) generation or genetic ablation of CD11b. Genetic elimination of the fibrinogen binding motif to CD11b reduced neuroinflammation, synaptic deficits, and cognitive decline in the 5XFAD mouse model of AD. Thus, fibrinogen-induced spine elimination and cognitive decline via CD11b link cerebrovascular damage with immune-mediated neurodegeneration and may have important implications in AD and related conditions.

 







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