Alzheimer's Disease as Longitudinal Coherence Failure: A General Theory of Regulated Stability (GTRS) Architecture for Multi-Mechanism Sequencing and Staged Intervention

Abstract Alzheimer’s disease (AD) is increasingly recognised as a multi-mechanism disorder, yet the field lacks a unified model that specifies the sequencing of mechanistic failures, the magnitude of each component’s contribution, and the causal priority among them. This paper applies the General Theory of Regulated Stability (GTRS) to map AD as a longitudinal coherence failure across ten coupled regulatory domains: glymphatic clearance, slow-wave sleep architecture, meningeal lymphatic drainage, cholinergic basal forebrain integrity, blood-brain barrier permeability, cerebral amyloid angiopathy, systemic (hepatic/renal) amyloid clearance, cardiovascular-metabolic risk loading, sex-specific vulnerability pathways, and age-dependent biomarker trajectories. Using the CDR (Coherence – Decoherence – Recoherence) temporal framework, the paper sequences these mechanisms across the decades-long preclinical window, identifies specific bifurcation points where regulatory node failure becomes self-reinforcing, and proposes an Individualised Education Program (IEP)-adapted intervention architecture for staged, adaptive clinical response. The paper positions AD not as a single-target pharmacological challenge but as a longitudinal regulatory erosion requiring the same individualised, monitored, adaptive methodology that has proven effective in developmental disability services. The GTRS framework provides the integrative architecture the field has called for; clinical specialists provide the domain expertise to populate it.