Evidence in favor of Braak staging of Parkinson's disease

Recently, Braak and coworkers proposed a pathologic staging scheme for Parkinson disease (PD). In this staging, scheme substantia nigra pathology occurs at midstage disease, while involvement of anterior olfactory nucleus, medulla, and pontine tegmentum occur earlier. In the last stages, Lewy bodies (LBs) involve cortical areas. The general principles of the proposed staging system have been confirmed in several studies of PD, but it does not appear to fit with all LB disorders. We studied the density and distribution of LBs with alpha-synuclein immunohistochemistry in normal elderly with incidental LBs (N = 12); progressive supranuclear palsy (PSP) with incidental LBs (N = 18); Lewy body disease (LBD) with minimal or no Alzheimer type pathology (N = 52); LBD with concomitant Alzheimer disease (AD) (N = 84); and cases of AD with amygdala predominant LBs (N = 64). The proportion of cases that fit the PD staging scheme was 67% for incidental LBs; 86% for PSP with LBs; 86% for pure LBD; and 84% for LBD with AD; but only 6% for AD with amygdala predominant LBs. The PD staging scheme is valid, except in the setting of advanced AD. In this situation, LBs may be unrelated to PD and more likely related to factors inherent to AD and the selective vulnerability of the amygdala to both Alzheimer and alpha-synuclein pathologies.