Parkinson’s disease (PD) is a multisystem disorder in which predisposed neuronal types in specific regions of the human peripheral, enteric, and central nervous systems become progressively involved. A staging procedure for the PD-related inclusion body pathology (i.e., Lewy neurites and Lewy bodies) in the brain proposes that the pathological process begins at two sites and progresses in a topographically predictable sequence in 6 stages. During stages 1–2, the inclusion body pathology remains confined to the medulla oblongata, pontine tegmentum, and anterior olfactory structures. In stages 3–4, the basal mid- and forebrain become the focus of the pathology and the illness reaches its symptomatic phase. In the final stages 5–6, the pathological process is seen in the association areas and primary fields of the neocortex. To date, we have staged a total of 301 autopsy cases, including 106 cases with incidental pathology and 176 clinically diagnosed PD cases. In addition, 163 age-matched controls were examined. 19 of the 301 cases with PD-related pathology displayed a pathological distribution pattern of Lewy neurites and Lewy bodies that diverged from the staging scheme described above. In these cases, olfactory structures and the amygdala were predominantly involved in the virtual absence of brain stem pathology. Most of the divergent cases (17/19) had advanced concomitant Alzheimer’s disease-related neurofibrillary changes (stages IV-VI).