This study investigates the role of acetylated α-Tubulin in the pathology of Parkinson’s disease (PD), focusing on its redistribution and its relationship with α-Synuclein aggregation. The research analyzed post-mortem human brain tissue from PD patients and control subjects, revealing that acetylated α-Tubulin redistributes in the neuronal cell bodies of subcortical structures, such as the substantia nigra, locus coeruleus, and dorsal motor nucleus of the vagus, but not in the cerebral cortex. This redistribution is associated with α-Synuclein oligomerization and phosphorylated Ser129 α-Synuclein, suggesting a potential model for Lewy body (LB) formation. High-resolution and 3D reconstruction analyses further linked acetylated α-Tubulin redistribution to α-Synuclein pathology, highlighting its involvement in the early stages of LB formation. The study also identified threadlike structures resembling tunneling nanotubes, which contain α-Synuclein oligomers and are associated with acetylated α-Tubulin-enriched neurons. These findings support the role of acetylated α-Tubulin in PD pathogenesis and LB formation, offering new insights into the mechanisms underlying α-Synuclein aggregation and neurodegeneration in PD.This study investigates the role of acetylated α-Tubulin in the pathology of Parkinson’s disease (PD), focusing on its redistribution and its relationship with α-Synuclein aggregation. The research analyzed post-mortem human brain tissue from PD patients and control subjects, revealing that acetylated α-Tubulin redistributes in the neuronal cell bodies of subcortical structures, such as the substantia nigra, locus coeruleus, and dorsal motor nucleus of the vagus, but not in the cerebral cortex. This redistribution is associated with α-Synuclein oligomerization and phosphorylated Ser129 α-Synuclein, suggesting a potential model for Lewy body (LB) formation. High-resolution and 3D reconstruction analyses further linked acetylated α-Tubulin redistribution to α-Synuclein pathology, highlighting its involvement in the early stages of LB formation. The study also identified threadlike structures resembling tunneling nanotubes, which contain α-Synuclein oligomers and are associated with acetylated α-Tubulin-enriched neurons. These findings support the role of acetylated α-Tubulin in PD pathogenesis and LB formation, offering new insights into the mechanisms underlying α-Synuclein aggregation and neurodegeneration in PD.