Investigate the role of neuroinflammation and microglial priming in the earliest stages of Alzheimer's Disease pathology, before clinical symptoms emerge. Key questions: 1. How do DAM (Disease-Associated Microglia) transition states differ between early and late AD? What triggers the transition? 2. What is the role of TREM2, P2RY12, and homeostatic microglial markers in early AD surveillance vs pathological priming? 3. How does complement activation (C1q, C3, CR3) drive synaptic pruning and neuroinflammation in prodromal AD? 4. Can microglial priming be reversed by anti-inflammatory interventions (TNF blockade, IL-6 inhibition, CSF1R modulation)? 5. What biomarkers best capture early neuroinflammatory state (plasma GFAP, YKL-40, sTREM2, CSF cytokines)? 6. How does APOE4 genotype alter microglial lipid metabolism and inflammatory priming in early AD?
Landscape Summary: Neuroinflammation and microglial priming in early Alzheimer's Disease is a 0.9 priority gap in neurodegeneration. It has 65 linked hypotheses with average composite score 0.672. Status: partially_addressed.
Colonna, Sevlever, et al. (TREM2 biology)
Neuroinflammation and microglial priming in early Alzheimer's Disease — INVOKE-2 (completed)
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