Hypothesis Comparison

graph TD
    A["APOE4 Gene rs429358 SNP"] -->|"encodes"| B["APOE4 Protein Arg112"]
    C["Base Editing CRISPR System"] -->|"converts T to C"| A
    D["Prime Editing Technology"] -->|"precision editing"| A
    B -->|"structural dysfunction"| E["Impaired Lipid Binding"]
    B -->|"altered conformation"| F["Reduced HDL Formation"]
    E -->|"disrupts"| G["Cholesterol Homeostasis"]
    F -->|"impairs"| H["Neuronal Membrane Repair"]
    G -->|"triggers"| I["Amyloid Beta Accumulation"]
    H -->|"leads to"| J["Tau Hyperphosphorylation"]
    I -->|"activates"| K["Neuroinflammation"]
    J -->|"causes"| L["Synaptic Dysfunction"]
    K -->|"promotes"| M["Neuronal Death"]
    L -->|"results in"| N["Cognitive Decline"]
    A -->|"converted to"| O["APOE3 Protective Variant Cys112"]
    O -->|"prevents"| P["Alzheimer Disease Progression"]

    classDef mechanism fill:#4fc3f7
    classDef pathology fill:#ef5350
    classDef therapy fill:#81c784
    classDef outcome fill:#ffd54f
    classDef genetics fill:#ce93d8

    class A,B,E,F,G,H genetics
    class C,D therapy
    class I,J,K,L,M mechanism
    class N,P outcome
    class O pathology

graph TD
    A["APOE4 Gene Expression"] --> B["APOE4 Protein Synthesis"]
    B --> C["Domain Interaction Formation<br/>Arg61-Glu255 Salt Bridge"]
    C --> D["Reduced Lipid Binding Affinity<br/>Impaired Lipidation"]
    D --> E["Unstable Lipoprotein Particles"]
    E --> F["Defective Cholesterol Transport"]
    F --> G["Neuronal Membrane Dysfunction"]
    E --> H["Increased Abeta Aggregation"]
    G --> I["Synaptic Degeneration"]
    H --> I
    I --> J["Cognitive Decline<br/>Alzheimer's Disease"]
    
    K["Lipidation Enhancement<br/>Therapeutic Intervention"] --> D
    K --> L["Stabilized APOE4-Lipid<br/>Complexes"]
    L --> M["Restored Cholesterol<br/>Homeostasis"]
    M --> N["Neuroprotection<br/>Cognitive Preservation"]
    L --> O["Enhanced Abeta Clearance"]
    O --> N