TREM2-dependent microglial processing of alpha-synuclein fibrils via AEP truncation

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Composite

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Description

PMID:39665233 showed microglia phagocytose alpha-synuclein fibrils via TREM2 and AEP cleaves them to truncated alpha-syn 1-103, enhancing pathogenicity. However, the complete signaling cascade from TREM2 activation to enhanced alpha-syn toxicity, the relative contributions of other TREM2 ligands (besides alpha-syn), and whether microglial AEP activity differs between PD patients and controls are unknown.

Evidence summary

Resolved by hypothesis h-var-08a4d5c07a: Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration. Score: 0.907. Supporting PMIDs: 33875891, 30610225, 31748742, 27519954, 33741860.

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