Gut/Brain Axis Studies

Braak's Hypothesis

Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen

Authors: H. Braak, U. Rüb, W. P. Gai, and K. Del Tredici

Publication date: March 5, 2003

Parkinson's disease is a condition where certain areas of the brain progressively deteriorate. This deterioration is linked to the formation of clumps of proteins (alpha-synuclein aggregation)  within specific types of brain cells. It starts in a part of the brainstem called the dorsal motor nucleus of the vagus nerve and then spreads upwards through other parts of the brain like the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain, eventually reaching the cerebral cortex. Over time, this leads to severe problems with functions like movement, emotions, and automatic bodily processes.

Interestingly, in some cases of Parkinson's, the disease may also affect the gut nervous system and the vagus nerve's dorsal motor nucleus. This observation, combined with the idea that the spread of brain damage in Parkinson's resembles a falling row of dominos, raises the question of whether Parkinson's might start outside the brain. There's a theory that a yet-to-be-identified germ or pathogen could enter the body through the gut, travel along nerve fibers connected to the vagus nerve, and then spread to the brain. This theory suggests that this pathogen could then move through nerve connections to specific areas of the brain, causing the sequential damage seen in Parkinson's disease.

In simple terms, the theory, termed Braak’s hypothesis,  proposes that Parkinson's might not just be a brain problem, but could start in the gut and move to the brain through nerve connections. This could explain why certain brain areas are affected in a specific order in Parkinson's disease.

This image shows the direction and pathway in which alpha-synuclein travels up the vagus nerve.