Fibrinogen induces spine elimination in Alzheimer’sApril 9, 2019
Mario Merlini et al unveiled the role of the blood-clotting protein fibrinogen in blood in causing the characteristic cognitive decline of Alzheimer’s disease. Cerebrovascular alterations are a key feature of Alzheimer’s disease (AD) pathogenesis. The researchers used state-of-the-art imaging technology to produce the first three-dimensional volume images of Alzheimer’s disease. The images of the brains of patients with Alzheimer’s disease and mouse models were studied. The blood-protein fibrinogen was seen to leak from the blood into the brain, where it activated the brain’s immune cells triggering them to destroy neuronal synapses. Fibrinogen then induces spine elimination leading to cognitive deficits mediated by CD11b-CD18 microglia activation. Fibrinogen-induced spine elimination was prevented by inhibiting reactive oxygen species (ROS) generation or by genetic elimination of CD11b. In the mouse models, this genetic elimination showed to reduce neuroinflammation, synaptic deficits and cognitive decline. The research thus unveils that fibrinogen-induced spine elimination and cognitive decline via CD11b leads to cerebrovascular damage with immune-mediated neurodegeneration and may have important implications in AD and related conditions.
Source: Neuron Feb 5,t 2019 DOI: https://doi.org/10.1016/j.neuron.2019.01.014