Hypothesis Comparison

graph TD
    subgraph Disease["Alzheimer's Disease Pathology"]
        A["Amyloid beta accumulation"] -->|"impairs"| B["Lysosomal dysfunction"]
        C["Tau protein aggregation"] -->|"disrupts"| B
        B -->|"reduces"| D["TFEB nuclear translocation"]
        D -->|"decreases"| E["CLEAR gene network expression"]
        E -->|"impairs"| F["Autophagy and proteostasis"]
        F -->|"worsens"| G["Neuronal degeneration"]
    end
    
    subgraph Intervention["Cell-Type Specific TFEB Modulation"]
        H["AAV vector delivery"] -->|"targets"| I["Neuron-specific promoter"]
        H -->|"targets"| J["Microglia-specific promoter"]
        I -->|"expresses"| K["Constitutively active TFEB"]
        J -->|"expresses"| K
        K -->|"translocates to"| L["Nucleus"]
    end
    
    subgraph Mechanisms["Molecular Mechanisms"]
        L -->|"activates"| M["CLEAR gene network"]
        M -->|"upregulates"| N["Lysosomal biogenesis"]
        M -->|"enhances"| O["Autophagy machinery"]
        N -->|"increases"| P["Protein degradation capacity"]
        O -->|"promotes"| P
    end
    
    subgraph Outcomes["Therapeutic Outcomes"]
        P -->|"clears"| Q["Amyloid beta plaques"]
        P -->|"degrades"| R["Tau aggregates"]
        P -->|"improves"| S["Mitochondrial quality control"]
        Q -->|"leads to"| T["Neuroprotection"]
        R -->|"leads to"| T
        S -->|"leads to"| T
    end

    style A fill:#ef5350,stroke:#333,color:#000
    style C fill:#ef5350,stroke:#333,color:#000
    style B fill:#ef5350,stroke:#333,color:#000
    style G fill:#ef5350,stroke:#333,color:#000
    style H fill:#81c784,stroke:#333,color:#000
    style I fill:#81c784,stroke:#333,color:#000
    style J fill:#81c784,stroke:#333,color:#000
    style K fill:#ce93d8,stroke:#333,color:#000
    style D fill:#4fc3f7,stroke:#333,color:#000
    style L fill:#4fc3f7,stroke:#333,color:#000
    style M fill:#4fc3f7,stroke:#333,color:#000
    style N fill:#4fc3f7,stroke:#333,color:#000
    style O fill:#4fc3f7,stroke:#333,color:#000
    style P fill:#4fc3f7,stroke:#333,color:#000
    style E fill:#4fc3f7,stroke:#333,color:#000
    style F fill:#4fc3f7,stroke:#333,color:#000
    style Q fill:#ffd54f,stroke:#333,color:#000
    style R fill:#ffd54f,stroke:#333,color:#000
    style S fill:#ffd54f,stroke:#333,color:#000
    style T fill:#ffd54f,stroke:#333,color:#000

graph TD
    A["Energy Stress/
Metabolic Demand"]
    B["mTORC1
Activation"]
    C["TFEB
Phosphorylation"]
    D["TFEB Nuclear
Translocation Blocked"]
    E["Reduced CLEAR
Network Expression"]
    F["Impaired Lysosomal
Biogenesis"]
    G["Autophagy
Dysfunction"]
    H["Mitochondrial
Damage Accumulation"]
    I["ATP Production
Decline"]
    J["Protein Aggregate
Accumulation"]
    K["Cellular
Dysfunction"]
    L["Neuronal
Death"]
    M["Neurodegeneration
Phenotype"]
    N["TFEB
Overexpression"]
    O["Lysosomal
Enhancement Therapy"]

    A -->|"activates"| B
    B -->|"phosphorylates"| C
    C -->|"prevents"| D
    D -->|"reduces"| E
    E -->|"decreases"| F
    E -->|"impairs"| G
    F -->|"limits"| G
    G -->|"fails to clear"| H
    H -->|"reduces"| I
    I -->|"feeds back to"| A
    G -->|"fails to degrade"| J
    H -->|"contributes to"| K
    J -->|"contributes to"| K
    K -->|"leads to"| L
    L -->|"causes"| M
    N -->|"restores"| E
    O -->|"enhances"| F

    classDef normal fill:#4fc3f7
    classDef therapeutic fill:#81c784
    classDef pathology fill:#ef5350
    classDef outcome fill:#ffd54f
    classDef molecular fill:#ce93d8

    class A,I normal
    class N,O therapeutic
    class B,C,D,E,F,G,H,J,K,L pathology
    class M outcome
    class A molecular