香港六合彩

During Alzheimer鈥檚 disease the connections between neurons, 鈥榮ynapses鈥� are lost, and this correlates strongly with cognitive decline. Loss of synapses can result from the dysfunctional activity of microglia, the resident brain immune cells, which are triggered to engulf synapses in the early stages of Alzheimer鈥檚, in a process called phagocytosis. The signals responsible for driving this process are not well understood.

In the new study, Dr Sebastiaan De Schepper, a postdoctoral fellow in the Hong lab and a Sir Henry Wellcome fellow, identified a role for a protein known as SPP1, or osteopontin, in mediating the loss of synapses in mouse models of Alzheimer鈥檚.

In mouse models where osteopontin was absent, microglia were prevented from engulfing synapses, indicating that the protein is required for microglial phagocytosis to take place.

In addition, Dr De Schepper and the team also showed for the first time that microglia interact with cells in the perivascular space, a fluid-filled structure that surrounds small blood vessels in the brain. They discovered that osteopontin is released by cells in the perivascular space, and acts as a signal to microglia to engulf synapses. These cells, known as perivascular macrophages, may act as a first line of defence against the formation of harmful amyloid-beta plaques in the blood vessels.

"We know that osteopontin is elevated in the spinal fluid of Alzheimer鈥檚 patients, but its function was previously unknown. Our study demonstrates a clear role for the protein in driving the dysfunctional activity of microglia which leads to synapse loss".听Dr Soyon Hong, Group Leader at the UK DRI at 香港六合彩

Dr Hong continued:听鈥淚t is becoming increasingly clear that the vascular space is central to Alzheimer鈥檚 disease pathology. In fact, blood vessels may represent an early and vulnerable site for amyloid-beta protein deposits to form. Our study suggests that this may be a trigger for an increase in osteopontin levels, which in turn leads to loss of neighbouring synapses and activation of microglia and other brain macrophages.鈥�

The team will now test ways to therapeutically target osteopontin in the early stages of Alzheimer鈥檚, aiming to prevent synapse loss and inflammation in the brain.

Links

• De Schepper, S., Ge, J.Z., Crowley, G.听et al.听.听Nat Neurosci听(2023).

Source

Image:

Dr De Schepper

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