Exploration of Neuroprotective Therapy

PD stages	α-Synuclein aggregate location	Signs/symptoms
Stage 1	Olfactory bulb, dorsal nucleus of vagus nerve, medulla oblongata, ENS, gut	Olfactory dysfunction, constipation, RBD
Stage 2	Lower brainstem, cerebral cortex	Lowered blood pressure, continued stage 1 symptoms
Stage 3	Midbrain, substantia nigra, amygdala	Cognitive impairment, thermoregulation disorder, continued stage 2 and previous symptoms
Stage 4	Amygdala, basal prosencephalon, mesocortex	Bradykinesia, resting tremor, rigidity, postural instability, continued stage 3 and previous symptoms
Stage 5	High order sensory association areas of neocortex, prefrontal neocortex	Motion fluctuation, fatigue, visual hallucinations, dementia, continued stage 4 and previous symptoms
Stage 6	First order sensory association areas of neocortex, premotor areas, primary sensory areas, primary motor field	Continued stage 5 and previous symptoms

PD stages

α-Synuclein aggregate location

Signs/symptoms

Stage 1

Olfactory bulb, dorsal nucleus of vagus nerve, medulla oblongata, ENS, gut

Olfactory dysfunction, constipation, RBD

Stage 2

Lower brainstem, cerebral cortex

Lowered blood pressure, continued stage 1 symptoms

Stage 3

Midbrain, substantia nigra, amygdala

Cognitive impairment, thermoregulation disorder, continued stage 2 and previous symptoms

Stage 4

Amygdala, basal prosencephalon, mesocortex

Bradykinesia, resting tremor, rigidity, postural instability, continued stage 3 and previous symptoms

Stage 5

High order sensory association areas of neocortex, prefrontal neocortex

Motion fluctuation, fatigue, visual hallucinations, dementia, continued stage 4 and previous symptoms

Stage 6

First order sensory association areas of neocortex, premotor areas, primary sensory areas, primary motor field

Continued stage 5 and previous symptoms