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Abstract This study investigates cerebellar neuropathology in idiopathic Parkinson's disease (iPD), focusing on the dentate nucleus (DN) and its adjacent white matter (DN-WM). Historically, iPD research has centered on basal ganglia dysfunction and neuronal Lewy bodies. However, we present evidence of significant oligodendrocytic α-synuclein (α-syn) pathology and neuronal hypertrophy within the DN of iPD patients, expanding the traditional understanding of the disease beyond the nigrostriatal system. Using immunohistochemistry (IHC), we systematically assessed α-syn-positive inclusions in autopsy-confirmed iPD brains compared to controls. We identified prominent intracytoplasmic α-syn inclusions within oligodendrocytes in the peri-dental WM, distinct from classic neuronal Lewy bodies, which were largely absent in the dentate neurons. Stereology-based morphometric analyses revealed significant hypertrophy of DN neuronal soma, nuclei, and nucleoli in iPD subjects.These findings suggest that oligodendrocytic α-synucleinopathy and associated white matter dysfunction in the cerebellum may contribute to both motor and non-motor symptoms in iPD. This highlights a critical, often underappreciated, role for cerebellar oligodendrocytes in disease pathogenesis, opening new avenues for therapeutic strategies targeting glial cells and white matter integrity.
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