By Natalie Lo ‘21

Alzheimer’s Disease (AD) is characterized by the formation of β-amyloid plaques Aβ, microglial activation, and inflammation in the brain. Microglia are immune cells found in the central nervous system (CNS). In AD, the blood-brain barrier is disrupted, which leads to bleeding, vascular damage, and an increase in blood proteins. Currently, there is an unknown relationship between vascular dysfunction, proteins like fibrinogen (a blood coagulation protein), and Aβ. The pathogenesis of AD has captured the attention of a group of scientists at the Gladstone Institute of Neurological Disease in San Francisco.

The group of researchers conducted in vivo 3D immunofluorescent labeling in 5XFAD mouse brains to examine Aβ deposits and fibrinogen. The study revealed that fibrinogen can be utilized as a detector for abnormalities in AD, and the data link the protein as a trigger for characteristics of AD, such as cognitive impairment, microglia-dependent spine elimination, and dendrite loss in regions with Aβ deposits. In the CNS, fibrinogen activates the microglia by binding to CD11b-CD18. Working with CD-11b may prevent the clearing of β-amyloid plaques, which may lead to further neurodegeneration. When the binding between fibrinogen and CD-11b is prevented genetically, the Aβ plaque decreases in the hippocampus, and thus neurodegeneration decreases. Furthermore, fibrinogen is enough to cause AD pathogenesis even without the presence of Aβ accumulation.

This study reveals more about the pathogenesis of Alzheimer’s disease, leading the medical field one step closer to finding the underlying cause of AD, and ultimately to discovering potential treatments for AD that target fibrin and help diminish cognitive disorders.

References

1. M. Merlini, et. al., Fibrinogen induces microglia-mediated spine elimination and cognitive impairment in an alzheimer’s disease model. Neuron 101, 1-10 (2019). doi:10.1016/j.neuron.2019.01.014l.  
2. Image retrieved from: https://openi.nlm.nih.gov/detailedresult.php?img=PMC2137908_jem2040571f08&req=4