Does SPP1-mediated synaptic engulfment represent beneficial clearance or pathological synapse loss in AD?

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Description

While SPP1 absence prevents synaptic loss, it’s unclear whether this represents loss of beneficial amyloid clearance or prevention of pathological synapse destruction. This fundamental question affects whether SPP1 should be therapeutically enhanced or inhibited in different disease stages.

Gap type: open_question Source paper: Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease. (2023, Nat Neurosci, PMID:36747024)

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