Evaluation of the Braak hypothesis: how far can it explain the pathogenesis of Parkinson's disease?

Braak's proposal that, in patients with Parkinson's disease, Lewy bodies and neurites progressively invade the brain through regions connected to autonomic and olfactory centers remains contentious. Confounding factors include the lack of an in vivo marker to examine the progression of Lewy pathology, the retrospective nature or absence of clinical information for many cross-sectional pathological datasets, and for those with limited disease (clinically or neuropathologically), the absence of information concerning additional conditions. Despite these data limitations at this time, the brain pathology for most patients with typical Parkinson's disease can be predicted using Braak's scheme. What this tells us about the pathogenesis of Parkinson's disease will be explored in this review.