Alpha-Synuclein Expression in the Developing Human Brain

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Abstract
Alpha (α)-synuclein is a presynaptic protein, abnormal expression of which has been associated with neurodegenerative and neoplastic diseases. It is abundant in the developing vertebrate central nervous system (CNS), but less is known about its developmental expression in the human CNS. Immunohistochemical expression of α-synuclein was studied in 39 fetal, perinatal, pediatric, and adolescent brains. Perikaryal expression of α-synuclein is observed as early as 11-wk gestation in the cortical plate. Several discrete neuronal groups in the hippocampus, basal ganglia, and brain stem express perikaryal α-synuclein by 20-wk gestation, persisting through the first few years of life. In the cerebellum, α-synuclein is present by 21-wk gestation and persists into adult life as a coarse granular neuropil reaction product in the internal granular layer, and as a diffuse neuropil “blush” in the molecular layer. The germinal matrix, glia, endothelial cells, external granular layer, Pukinje cells, and dentate neurons are consistently negative for α-synuclein. We conclude that α-synuclein is expressed very early in human gestation, and that its distribution and temporal sequence of expression varies in discrete neuronal groups. Perikaryal α-synuclein starts disappearing from the neuronal cytosol in early childhood, and only the neuropil retains immunoreactivity into adulthood. The reappearance of α-synuclein in the adult neuronal cytosol in certain disease processes may represent reemergence of cues from an earlier developmental stage as part of a stress response.