In 2003 Heiko Braak's group proposed that Lewy pathology climbs through the brain in six stages: from the lower brainstem and the smell pathway, through the substantia nigra, to the cortex. 41 A newer model splits Parkinson's into a body-first type that starts in the gut and a brain-first type that starts inside the brain. 37 Step through each order and watch which symptoms tend to go with it.
ModelLayer
Schematic midline view. Deep and lateral structures are projected onto it and dashed.
Where Braak does not fit
Braak's scheme came from a selected sample: incidental cases and people with a clinical diagnosis, cut in unusually thick sections. 42 Other brain banks tested it on their own cases. Pick a study to see how many brains followed the expected bottom-to-top order.
Study
Each square is 1% of the brains in that study. Rounded to whole squares.
Beyond dopamine: the other systems hit
Lewy pathology and cell loss reach far beyond the substantia nigra: noradrenaline, serotonin and acetylcholine cells in the brain, and nerves in the heart, the gut and the skin. These help explain the symptoms that levodopa does not touch, covered in Beyond movement. Pick a system.