Coping Equilibrium and Stability Margins: -Level Reinterpretation of Alzheimer's Disease

Abstract Alzheimer's disease (AD) remains one of the most challenging neurodegenerative disorders despite decades of intensive molecular research. Current pathological models successfully describe numerous disease-associated mechanisms, including amyloid-β accumulation, tau pathology, mitochondrial dysfunction, impaired glucose metabolism and chronic neuroinflammation. Nevertheless, therapies targeting these individual mechanisms have produced only modest clinical benefit, suggesting that they may represent downstream manifestations rather than the primary organizing principle of disease progression. This paper introduces the Ruin Horizon Framework (RHF) as a systems-level stability architecture for interpreting Alzheimer's disease. Rather than considering AD as the consequence of isolated molecular abnormalities, RHF proposes that disease progression reflects the gradual erosion of the brain's global stability reserve. Within this framework, neuronal function depends on the continuous ability of the network to absorb perturbations while maintaining functional organization. Progressive metabolic impairment, increasing inflammatory burden, impaired energy utilization and signaling noise collectively reduce this reserve until a critical stability threshold—the Ruin Horizon—is approached. The RHF does not replace established molecular pathology but reorganizes existing evidence into a unified dynamical framework. Amyloid deposition, tau pathology and neuroinflammation are interpreted as interacting components of a broader network destabilization process rather than independent initiating events. This perspective also provides a potential explanation for the limited clinical efficacy of single-target therapeutic strategies. The framework generates several experimentally testable predictions, including the existence of a prolonged pre-instability phase characterized by declining network resilience before irreversible neurodegeneration occurs. If validated, RHF may provide a theoretical basis for predictive diagnostics and multi-domain stabilization strategies aimed at preserving neuronal viability rather than targeting isolated molecular abnormalities