α-Synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects

Studies on cases with incidental Lewy body disease (ILBD) suggest that alpha-synuclein (alpha SN) pathology of Parkinson's disease (PD) starts in lower brainstem nuclei and in the olfactory bulb. However, medullary structures as the induction site of alpha SN pathology have been questioned as large parts of the nervous system, including the spinal cord and the peripheral autonomic nervous system (PANS), have not been examined in ILBD. Thus, the time course of PD lesions in the spinal cord or PANS in relation to medullary lesions remains unknown. We collected 98 post mortem cases with no reference to PD-associated symptoms on clinical records. alpha SN pathology was found in the central nervous system, including the spinal cord, and in the PANS in 17 (17.3%) cases. alpha SN pathology was encountered in autonomic nuclei of the thoracic spinal cord, brainstem and olfactory nerves in 17/17, in sacral parasympathetic nuclei in 15/16, in the myenteric plexus of oesophagus in 14/17, in sympathetic ganglia in 14/17, and in the vagus nerve in 12/16 cases. In addition to the thoracic lateral horns, a high number of alpha SN lesions was also found in non-autonomic spinal cord nuclei. Considering supraspinal structures our cases corresponded roughly to the recently described sequential order of alpha SN involvement in PD. Our study indicates, however, that the autonomic nuclei of the spinal cord and the PANS belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves. A larger cohort of ILBD cases will be needed to pinpoint the precise induction site of alpha SN pathology among these structures.