alpha-Synuclein pathology in the neostriatum in Parkinson's disease

We immunohistochemically examined the neostriatum from 25 patients with symptomatic and presymptomatic Parkinson's disease (PD) with various degrees of Lewy body pathology, using anti-phosphorylated alpha-synuclein (alphaS) antibody. These patients were classified according to the PD staging proposed by Braak et al. (Neurobiol Aging 24:197-211, 2003): stage II (alphaS pathology confined to the medulla oblongata and pontine tegmentum), stage III (alphaS pathology confined to the brainstem), stage IV (limbic stage), and stages V and VI (neocortical stage). alphaS immunohistochemistry revealed neuronal and glial cytoplasmic inclusions and neuritic changes in the neostriatum. alphaS inclusions were found in the medium-sized neurons (GABAergic neurons that project to the globus pallidus) and large neurons (cholinergic interneurons); the former began to appear at stage III and the latter was noted at stages V and VI. Neuritic changes and glial inclusions also began to appear at stage III. The numbers of neuronal and glial inclusions, and the extent of neuritic changes, correlated with the PD stage (P < 0.001). These findings suggest that intrinsic neostriatal neurons degenerate through alphaS aggregation during PD progression.