Progression and staging of Lewy pathology in brains from patients with dementia with Lewy bodies

Using alpha-synuclein-immunohistochemistry, 27 brains of dementia with Lewy bodies (DLB) were investigated to identify the progression of Lewy pathology including Lewy bodies (LB) and LB-related neurites in the cerebrum. The numbers of alpha-synuclein-positive LB and LB-related neurites were semiquantitatively evaluated in the amygdala, hippocampus, entorhinal cortex, transentorhinal cortex, insular cortex, middle temporal cortex and superior frontal cortex. The results indicated that Lewy pathology within the neuron progresses first in the axonal terminal, subsequently in the cell body and finally in the dendrite, that Lewy pathology in the cerebral cortex progresses first in layers V-VI, subsequently in layer III and finally in layer II, and that Lewy pathology in the cerebrum progresses first in the amygdala, subsequently in the limbic cortex and finally in the neocortex. In addition, Lewy pathology was graded from stage I to stage IV based on the progression of Lewy pathology. The 27 brains examined were classified into 3 brains showing stage I, 11 showing stage II, 7 showing stage III and 6 showing stage IV. Comparing these stages with the pathological subtypes of DLB brains, brains of the subtype showing severe Alzheimer pathology corresponded to brains showing an advanced stage, suggesting that Alzheimer pathology exacerbates Lewy pathology.