Alzheimer’s disease (AD) is increasingly understood as a dynamic systems disorder marked by phase-wise regulatory failure, rather than a linear cascade of protein aggregation. This article conceptualizes AD progression as a sequence of dysregulated homeostatic transitions—beginning with subtle failures in glutamate clearance, redox balance, and oscillatory coherence. As compensatory mechanisms exhaust, neuroglial systems enter an immunometabolic reaction phase characterized by microglial priming, astrocytic polarity loss, and mitochondrial instability. The brain adapts by simplifying network architecture and reducing synaptic plasticity, conserving energy at the expense of cognitive flexibility. Over time, this culminates in a pathological homeostasis: a maladaptive, energy-constrained equilibrium sustained by chronic neuroinflammation, proteostatic overload, and disrupted circadian–glymphatic coupling. Within this framework, AD represents a systemic breakdown in dynamic regulation— where resilience is gradually replaced by rigidity, clearance by accumulation, and cognition by compensation.
Multiple Sclerosis (MS) is characterized as a breakdown in dynamic regulatory coherence across immune, glial, and neural systems. Viewed as a sequence of phase transitions shaped by temporal delay, spatial compartmentalization, and energetic imbalance, MS reflects a shift from compartmentalized immune homeostasis to pathological amplification — driven by breach of CNS immune privilege, glial misregulation, and maladaptive metabolic reorganization.
Core disruptions begin with molecular mimicry and peripheral immune activation, leading to loss of blood–brain barrier integrity and infiltration of autoreactive T and B cells. This triggers a cascade of microglial priming, astrocytic gliosis, and oligodendrocyte stress. Persistent cytokine signaling (IL-1β, IL-6, IFN-γ, TNF-α) overwhelms cellular buffering capacity, destabilizing energetic efficiency and initiating a phase loop of neuroinflammation, demyelination, and incomplete repair.
Over time, reactive plasticity becomes rigid: remyelination fails, synaptic remodeling misfires, and axons degenerate under sustained metabolic burden. The system transitions into a refined pathological homeostasis—stable yet dysfunctional—where neuroimmune feedback is self-sustaining, neuroplasticity is constrained, and the CNS remains locked in a high-entropy, low-adaptability state.
In this framework, MS is not a static autoimmune event but a temporally disjointed, spatially compartmentalized failure of multiscale regulation. Therapeutic strategies must target not only immune suppression, but glial re-alignment, metabolic resilience, and the restoration of phase synchrony across biological systems.