alpha-synuclein and Spinal-Cord-Diseases

Parkinson's disease (PD) has traditionally ascribed to alpha-synucleinopathy of the substantia nigra; however, several studies have showed widespread alpha-synucleinopathy inside and outside the brain. The potential role of the spinal cord in the genesis of some symptoms has been quite neglected despite the frequent and precocious presence of alpha-synucleinopathy in the spinal cord of PD patients. We examined the literature about the pathology of the spinal cord in PD and the possible relevance of this pathology in the genesis of some nonmotor symptoms including urinary, sexual, and gastrointestinal, as well as of some motor symptoms.

Topics: alpha-Synuclein; Animals; Humans; Parkinson Disease; Spinal Cord; Spinal Cord Diseases

In this autopsy-based study, α-synuclein immunohistochemistry and lipofuscin pigment-Nissl architectonics in serial sections of 100 μm thickness were used to investigate the spinal cords and brains of 46 individuals: 28 patients with clinically and neuropathologically confirmed Parkinson's disease, 6 cases with incidental Lewy body disease, and 12 age-matched controls. α-Synuclein inclusions (particulate aggregations, Lewy neurites/bodies) in the spinal cord were present between neuropathological stages 2-6 in all cases whose brains were staged for Parkinson's disease-related synucleinopathy. The only individuals who did not have Lewy pathology in the spinal cord were a single stage 1 case (incidental Lewy body disease) and all controls. Because the Parkinson's disease-related lesions were observable in the spinal cord only after Lewy pathology was seen in the brain, it could be concluded that, within the central nervous system, sporadic Parkinson's disease does not begin in the spinal cord. In addition: (1) α-Synuclein-immunoreactive axons clearly predominated over Lewy bodies throughout the spinal cord and were visible in medial and anterior portions of the anterolateral funiculus. Their terminal axons formed dense α-synuclein-immunoreactive networks in the gray matter and were most conspicuous in the lateral portions of layers 1, 7, and in the cellular islands of layer 9. (2) Notably, this axonopathy increased remarkably in density from cervicothoracic segments to lumbosacral segments of the cord. (3) Topographically, it is likely that the spinal cord α-synuclein immunoreactive axonal networks represent descending projections from the supraspinal level setting nuclei (locus coeruleus, lower raphe nuclei, magnocellular portions of the reticular formation). (4) Following the appearance of the spinal cord axonal networks, select types of projection neurons in the spinal cord gray matter displayed α-synuclein-immunoreactive inclusions: chiefly, nociceptive neurons of the dorsal horn in layer 1, sympathetic and parasympathetic preganglionic neurons in layer 7, the cellular pools of α-motoneurons in layer 9, and the smaller motoneurons in Onuf's nucleus in layer 9 (ventral horn). The spinal cord lesions may contribute to clinical symptoms (e.g., pain, constipation, poor balance, lower urinary tract complaints, and sexual dysfunction) that occur during the premotor and motor phases of sporadic Parkinson's disease.

Topics: Aged; Aged, 80 and over; alpha-Synuclein; Biopsy; Brain; Case-Control Studies; Female; Humans; Lewy Body Disease; Male; Middle Aged; Neurites; Neurons; Parkinson Disease; Postmortem Changes; Spinal Cord; Spinal Cord Diseases

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

Topics: Age Factors; Aged, 80 and over; alpha-Synuclein; Autonomic Nervous System; Brain; Brain Diseases; Cohort Studies; Female; Finland; Humans; Immunohistochemistry; Male; Neuropil; Sacrococcygeal Region; Severity of Illness Index; Spinal Cord; Spinal Cord Diseases; Thoracic Vertebrae