An astrocyte-microglia MFG-E8 axis promotes synapse engulfment in early amyloid pathology.

In a mouse model of amyloidosis, early bulbous astrocytes in vulnerable regions are linked to higher MFG-E8 and increased local microglial synapse engulfment.

• Why it matters: Region-specific synapse loss occurs early in Alzheimer’s disease, but the upstream astrocyte signals that make synapses vulnerable are not well defined.
• What they did: The study profiled an early astrocyte state before widespread plaque deposition, then used astrocyte-specific gain- and loss-of-function to test whether astrocyte-derived MFG-E8 drives microglial engulfment via microglial β3 integrin signaling.
• The result: Astrocytic Mfge8 deletion reduced microglial engulfment and synapse loss across amyloidosis models and was associated with less amyloid pathology, gliosis, and cognitive impairment.

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