α-Synuclein pathology in the spinal cord autonomic nuclei associates with α-synuclein pathology in the brain: a population-based Vantaa 85+ study

In most subjects with Parkinson’s disease and dementia with Lewy bodies, α-synuclein (αS) immunoreactive pathology is found not only in the brain but also in the autonomic nuclei of the spinal cord. However, neither has the temporal course of αS pathology in the spinal cord in relation to the brain progression been established, nor has the extent of αS pathology in the spinal cord been analyzed in population-based studies. Using immunohistochemistry, the frequency and distribution of αS pathology were assessed semiquantitatively in the brains and spinal cord nuclei of 304 subjects who were aged at least 85 in the population-based Vantaa 85+ study. αS pathology was common in the spinal cord; 102 (34%) subjects had classic αS pathology in the thoracic and/or sacral autonomic nuclei. Moreover, 134 (44%) subjects showed grain- or dot-like immunoreactivity in neuropil (mini-aggregates) without classic Lewy neurites or Lewy bodies (LBs). The latter type of αS accumulation is associated with age, but also the classic αS pathology was found more often in the oldest compared to the youngest age group. The severity of αS pathology in the spinal cord autonomic nuclei is significantly associated with the extent and severity of αS pathology in the brain. Of the subjects, 60% with moderate to severe thoracic αS pathology and up to 89% with moderate to severe sacral αS pathology had diffuse neocortical type of LB pathology in the brain. αS pathology exclusively in the spinal cord was rare. Our study indicates that in general αS pathology in the spinal cord autonomic nuclei is associated with similar pathology in the brain.