Fig. 4

Schematic diagrams illustrating the neuropathological staging systems for LBD. The Newcastle-McKeith criteria distinguishes between brainstem predominant (regions affected including IX/X motor nucleus, locus coeruleus, and substantia nigra), limbic (transitional, regions include amygdala, transentorhinal cortex, and cingulate cortex), and diffuse neocortical (frontal, temporal, parietal, lobes are affected). N.B. the most recent consensus included the addition of olfactory only, and amygdala predominant stages [11] (a). Braak staging of α-syn deposition: Braak stage 1, IX/X motor nucleus of the medulla oblongata, Braak stage 2, addition of lesions to the locus coeruleus, Braak stage 3, α-syn progresses to the substantia nigra of the midbrain, Braak stage 4, α-syn lesions now detected in the transentorhinal region and CA2 of the hippocampus, Braak stage 5, higher association of the neocortex are affected, and Braak stage 6, α-syn is visible in the premotor and motor regions [139] (b). Leverenz and colleagues modified the original Newcastle-McKeith criteria to include cases that lack α-syn pathology in any other regions with the exception of the amygdala, known as amygdala predominant LB disease [140] (c). Beach and colleagues proposed a unified staging system to include cases that have α-syn confined to the olfactory bulb or bypass the brainstem to the limbic predominant pathway [41] (d)