Figure 1.

Schematic of the theory of multipathology convergence to neuronal stress leading to AD. In homeostasis, neuronal stress is low. Repeated traumatic brain injuries (TBI) may transiently increase neuronal stress in the CNS, but the levels of stress return back to homeostasis naturally. When a severe central or peripheral chronic condition occurs, the level of neuronal stress increases to an allostatic state, which may combine with TBI. Over time, additional chronic conditions stack up on top of the first condition to continually increase CNS neuronal stress up to the disease state. If there is no TBI in the life of a given patient, then the levels of neuronal stress follow the dashed line. Currently, there are no FDA-approved AD therapeutic intervention to guide the conversion from allostasis back to homeostasis, thus most patients progress to disease state.