Expression of Monomeric Alpha Synuclein in the Human Brainstem

Alpha-synuclein is a presynaptic protein abundantly expressed across the nervous system, implicated in synaptic vesicle dynamics, dopamine metabolism, and the assembly of the SNARE complex. Its aggregated forms are well-established hallmarks of neurodegenerative diseases, such as Parkinson's disease. However, the precise regional and cellular distribution of its physiological monomeric form across the human brainstem remains uncharacterized. This study aims to map the expression pattern of monomeric alpha-synuclein across the major segments of the human brainstem: the midbrain, pons, and medulla oblongata. Post-mortem human tissue sections deriving from the Body Donation Program of the University of Padova underwent immunohistochemical staining using antibodies selective for the monomeric conformation. Staining patterns were analyzed with respect to neuroanatomical localization, cellular morphology, and relative expression intensity across distinct nuclei, fiber tracts, and neuropil. Results revealed a heterogeneous distribution of monomeric alpha-synuclein, with notable expression in dorsal medulla, basal pons, and substantia nigra. Regional differences in staining intensity suggest that alpha-synuclein expression is tightly regulated in a structure-specific manner. These findings contribute to a deeper understanding of the normal physiological role of native alpha-synuclein in the brainstem and provide a valuable baseline for future research into its pathological forms in neurodegenerative disease.