Neuropathological and Biochemical Profiles of Lewy Pathology in the Central and Peripheral Nervous Systems of an Autopsy Case of SNCA Duplication.

Multiplication of the α-synuclein gene (SNCA) can cause familial Parkinson's disease (PD). In the present study, we investigated the neuropathological and biochemical profiles in the central and peripheral nervous systems of an autopsy case with SNCA duplication. The patient began to show gait disturbance and resting tremors at the age of 34. The motor symptoms of the patient responded well to levodopa therapy. However, the condition progressed to Hoehn and Yahr stage V at age 44, and the patient died of toxic shock syndrome at age 46. Post-mortem neuropathological examination revealed some common features of SNCA duplication, such as prominent neuronal loss in the substantia nigra and locus coeruleus, and widespread Lewy pathology from the brainstem to the neocortex. Marked Lewy neurites were also observed in the cornu Ammonis 2/3 region of the hippocampus; however, without apparent neuronal loss. Large Lewy bodies were frequently observed in the tuberomammillary nucleus of the hypothalamus. Additionally, Lewy pathology was frequently visible in the peripheral nervous system, including the sympathetic and dorsal root ganglia. Western blotting revealed bands, and immunoelectron microscopy analyses showed filaments typical of Lewy body disease in the central and peripheral nervous systems. These results show that duplication of the SNCA gene facilitates the formation of Lewy bodies in the central and peripheral nervous systems. These Lewy bodies show the same biochemical profiles as sporadic Lewy body disease.