Hypothesis Comparison

graph TD
    SST["SST gene<br/>somatostatin interneurons"] --> PV["PV+ interneurons<br/>parvalbumin positive"]
    PV --> GAMMA_GEN["Gamma oscillation<br/>generation 40Hz"]
    GAMMA_GEN --> HIPP_SYNC["Hippocampal<br/>gamma rhythm"]
    GAMMA_GEN --> CORT_SYNC["Cortical<br/>gamma rhythm"]
    
    AMYLOID["Amyloid beta<br/>accumulation"] --> GAMMA_RED["Reduced gamma power<br/>40-70% decrease"]
    TAU["Tau pathology<br/>neurofibrillary tangles"] --> GAMMA_RED
    
    GAMMA_RED --> DESYNC["Hippocampal-cortical<br/>desynchronization"]
    DESYNC --> MEM_IMP["Memory impairment<br/>encoding and retrieval"]
    
    GET["Gamma entrainment<br/>therapy 40Hz"] --> GAMMA_REST["Gamma rhythm<br/>restoration"]
    GAMMA_REST --> SYNC_REC["Synchrony recovery<br/>between regions"]
    SYNC_REC --> MEM_IMPROVE["Memory function<br/>improvement"]
    
    HIPP_SYNC --> SYNC_NORM["Normal hippocampal-<br/>cortical synchrony"]
    CORT_SYNC --> SYNC_NORM
    SYNC_NORM --> MEM_NORM["Normal memory<br/>function"]

    style SST fill:#ce93d8
    style PV fill:#4fc3f7
    style GAMMA_GEN fill:#4fc3f7
    style HIPP_SYNC fill:#4fc3f7
    style CORT_SYNC fill:#4fc3f7
    style SYNC_NORM fill:#4fc3f7
    style MEM_NORM fill:#4fc3f7
    style AMYLOID fill:#ef5350
    style TAU fill:#ef5350
    style GAMMA_RED fill:#ef5350
    style DESYNC fill:#ef5350
    style MEM_IMP fill:#ef5350
    style GET fill:#81c784
    style GAMMA_REST fill:#81c784
    style SYNC_REC fill:#ffd54f
    style MEM_IMPROVE fill:#ffd54f

graph TD
    A["Cellular Stress and DNA Damage"]
    B["Astrocyte Senescence Induction"]
    C["SASP Activation"]
    D["Pro-inflammatory Cytokine Release"]
    E["TNF-alpha and IL-1beta Secretion"]
    F["NF-kappaB Pathway Activation"]
    G["AQP4 Polarity Loss"]
    H["Dystroglycan Complex Disruption"]
    I["Glymphatic System Dysfunction"]
    J["Amyloid-beta Accumulation"]
    K["Tau Protein Aggregation"]
    L["Neuroinflammation Amplification"]
    M["Neuronal Death"]
    N["Cognitive Decline"]
    O["Anti-SASP Therapy"]
    P["AQP4 Restoration"]

    A -->|"oxidative stress"| B
    B -->|"senescence markers"| C
    C -->|"inflammatory cascade"| D
    D -->|"cytokine production"| E
    E -->|"signaling activation"| F
    F -->|"transcriptional changes"| G
    G -->|"membrane disruption"| H
    H -->|"clearance impairment"| I
    I -->|"protein accumulation"| J
    I -->|"protein misfolding"| K
    J -->|"toxic aggregates"| L
    K -->|"neurofibrillary tangles"| L
    L -->|"cell death pathways"| M
    M -->|"functional loss"| N
    O -->|"senolytic treatment"| C
    O -->|"polarity rescue"| P

    subgraph INITIATION["Senescence Initiation"]
        A
        B
        C
    end

    subgraph SASP["SASP Cascade"]
        D
        E
        F
    end

    subgraph AQP4_DYSFUNCTION["AQP4 Dysfunction"]
        G
        H
        I
    end

    subgraph PATHOLOGY["Neurodegenerative Pathology"]
        J
        K
        L
        M
        N
    end

    subgraph THERAPY["Therapeutic Intervention"]
        O
        P
    end

    style A fill:#4fc3f7
    style B fill:#ef5350
    style C fill:#ef5350
    style D fill:#ef5350
    style E fill:#ef5350
    style F fill:#ef5350
    style G fill:#ef5350
    style H fill:#ef5350
    style I fill:#ef5350
    style J fill:#ef5350
    style K fill:#ef5350
    style L fill:#ef5350
    style M fill:#ef5350
    style N fill:#ffd54f
    style O fill:#81c784
    style P fill:#81c784