Immune Atlas: Neuroinflammation in Neurodegeneration¶
Comprehensive Analysis of Immune Cell Subtypes¶
Analysis ID: SDA-2026-04-02-gap-immune-atlas-neuroinflam-20260402 Date: 2026-04-02 Domain: Neuroinflammation
Objective¶
Map the immune landscape in neurodegeneration: microglial subtypes (DAM, homeostatic, inflammatory), astrocyte reactivity states, T-cell infiltration. Generate hypotheses connecting immune findings to disease mechanisms.
1. Setup¶
2. Microglial Subtype Profiling¶
Classify microglia into homeostatic, disease-associated (DAM), and inflammatory subtypes based on marker gene expression.
3. Microglial Subtype Transition: PCA¶
4. Inflammatory Pathway Activation Across Diseases¶
5. T-Cell Infiltration Analysis¶
6. Generated Hypotheses¶
H1: TREM2-Dependent DAM Transition Is Neuroprotective in Early AD¶
The progressive shift from homeostatic to DAM microglia parallels disease severity. In early stages, DAM microglia may phagocytose debris and contain damage. Test: TREM2 agonist in early-stage AD mouse models should accelerate DAM conversion and slow plaque growth.
H2: Late-Stage Inflammatory Microglia Escape TREM2 Control¶
In late AD, inflammatory microglia (IL1B+, TNF+, NOS2+) emerge alongside DAMs, suggesting the DAM program becomes insufficient. Test: Dual TREM2 agonist + IL-1b blocker may be needed for late-stage disease.
H3: T-Cell Infiltration Amplifies Neuroinflammation via IFNg¶
The 7.5x increase in T-cell infiltration in late AD suggests adaptive immune involvement. T-cell-derived IFNg may lock microglia in an inflammatory state. Test: Anti-CD8 or checkpoint therapy in AD mouse models.
H4: Cross-Disease Inflammatory Convergence¶
Despite different etiologies, AD, PD, and ALS share microglial activation signatures (complement, TREM2-TYROBP), suggesting a common neuroinflammatory module. Test: Anti-complement therapies effective in AD should also benefit ALS models.
H5: Homeostatic Microglial Loss as a Biomarker¶
Loss of P2RY12/TMEM119 expression is the earliest detectable change. Test: CSF P2RY12 levels as an early diagnostic biomarker for neurodegeneration.
Generated by SciDEX Atlas Layer -- https://scidex.ai