**SASP-Mediated Complement Cascade Amplification in Alzheimer's Disease**
**Overview: Senescence, Inflammation, and Synaptic Loss**
Cellular senescence—a state of irreversible growth arrest accompanied by a pro-inflammatory secretome—accumulates dramatically with age and in Alzheimer's disease. Senescent astrocytes and microglia secrete the senescence-associated secretory phenotype (SASP), a cocktail of cytokines, chemokines, proteases, and critically, complement cascade initiators including C
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.75
Evidence
0.70
Novelty
0.85
Feasibility
0.75
Impact
0.80
Druggability
0.85
Safety
0.60
Competition
0.80
Data
0.75
Reproducible
0.70
Score Breakdown
Dimension
SASP-Mediated Complement Casca
Mechanistic
0.750
Evidence
0.700
Novelty
0.850
Feasibility
0.750
Impact
0.800
Druggability
0.850
Safety
0.600
Competition
0.800
Data
0.750
Reproducible
0.700
Evidence
SASP-Mediated Complement Cascade Amplification
Supporting Evidence
C1q and C3 mediate early synapse loss in AD mouse models; C1q/C3 knockout preserves synapsesPMID:27033548Science 2016
CR3 (CD11b/CD18) on microglia mediates complement-tagged synapse phagocytosisPMID:34472455Neural Regen Res 2021
Senescent astrocytes secrete high levels of C1q and C3 as part of SASP in aged and AD brainsPMID:35236834Nat Commun 2022
Senolytic treatment reduces brain C1q/C3 levels and preserves synaptic density in APP/PS1 micePMID:37384704Nat Aging 2023