flowchart TD
    A["APOE4 Microglial Cellular Architecture Defects<br/>MAM Mitochondria-ER Contact Sites"]
    B["VDAC1 Outer Membrane Channel<br/>Mitochondrial Calcium Entry"]
    C["GRP75 Chaperone Bridge<br/>VDAC1-IP3R1 Tether"]
    D["IP3R1 ER Calcium Channel<br/>Endoplasmic Reticulum Release"]
    E["MAM Complex Destabilized<br/>VDAC1-GRP75-IP3R1 Disrupted"]
    F["Mitochondrial Calcium Signaling Impaired<br/>ATP Synthesis Uncoupled"]
    G["Metabolic Flexibility Lost<br/>Energy Crisis Worsens"]
    H["VDAC1-IP3R1 Stabilizer Treatment<br/>Pharmacological MAM Restoration"]
    I["Mitochondria-ER Communication Restored<br/>Microglial Metabolic Rescue"]
    A --> E
    B --> C
    C --> D
    E -.->|"disrupts"| B
    E --> F
    F --> G
    H --> C
    H --> I
    style E fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
    style I fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7