A new unifying theory of Alzheimer’s disease is being put forward as an attempt to reconcile competing explanations for how the condition first emerges in the brain. Instead of treating each hypothesis as a rival, the framework links classic protein pathology with large-scale circuit failure and cellular stress.

At its core, the model suggests that impaired clearance of amyloid beta and pathological aggregation of tau protein trigger a cascade that destabilizes synaptic plasticity and disrupts functional connectivity across brain networks. These molecular changes, combined with chronic neuroinflammation and oxidative stress, increase neural entropy and gradually erode the brain’s capacity to maintain homeostasis.

The theory integrates earlier ideas such as the amyloid cascade hypothesis and the role of metabolic dysfunction, proposing that they are different faces of the same process rather than mutually exclusive stories. By tying together protein misfolding, glial activation, and network-level dysregulation, it aims to explain why some individuals remain cognitively resilient despite similar plaque loads, and why clinical symptoms only appear once a tipping point in systems-level failure is reached.