Bidirectional interplay between the brain and the gut includes the vagus nerve pathway, and non-vagus nerve pathways such as the bloodstream. Important factors associated with the development of PD include ageing-related processes, aggregation and spread of alpha-synuclein, gut bacterial microbiome and their metabolic activities, gut barrier disruption, inflammation, environmental influences, host genetic factors, and probably chance effects.
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In brain-first patients (bottom panel), the dopamine system starts to degenerate early
Characteristics of proposed body-first and brain-first subtypes of Parkinson’s disease
The body-first and brain-first model suggests that the clinical subtype with mild or no “bodily symptoms” before diagnosis reflects a brain-first origin of the disease