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, alpha-synuclein (alpha S) 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 alpha S pathology in the spinal cord in relation to the brain progression been established, nor has the extent of alpha S pathology in the spinal cord been analyzed in population-based studies. Using immunohistochemistry, the frequency and distribution of alpha S 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. alpha S pathology was common in the spinal cord; 102 (34%) subjects had classic alpha S 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 alpha S accumulation is associated with age, but also the classic alpha S pathology was found more often in the oldest compared to the youngest age group. The severity of alpha S pathology in the spinal cord autonomic nuclei is significantly associated with the extent and severity of alpha S pathology in the brain. Of the subjects, 60% with moderate to severe thoracic alpha S pathology and up to 89% with moderate to severe sacral alpha S pathology had diffuse neocortical type of LB pathology in the brain. alpha S pathology exclusively in the spinal cord was rare. Our study indicates that in general alpha S pathology in the spinal cord autonomic nuclei is associated with similar pathology in the brain.