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Converging Patterns of α-Synuclein Pathology in Multiple System Atrophy
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Journal Article
Converging Patterns of α-Synuclein Pathology in Multiple System Atrophy
2018
Overview
Abstract
We aimed to determine patterns of α-synuclein (α-syn) pathology in multiple system atrophy (MSA) using 70-µm-thick sections of 20 regions of the central nervous system of 37 cases with striato-nigral degeneration (SND) and 10 cases with olivo-ponto-cerebellar atrophy (OPCA). In SND cases with the shortest disease duration (phase 1), α-syn pathology was observed in striatum, lentiform nucleus, substantia nigra, brainstem white matter tracts, cerebellar subcortical white matter as well as motor cortex, midfrontal cortex, and sensory cortex. SND with increasing duration of disease (phase 2) was characterized by involvement of spinal cord and thalamus, while phase 3 was characterized by involvement of hippocampus and amygdala. Cases with the longest disease duration (phase 4) showed involvement of the visual cortex. We observed an increasing overlap of α-syn pathology with increasing duration of disease between SND and OPCA, and noted increasingly similar regional distribution patterns of α-syn pathology. The GBA variant, p.Thr408Met, was found to have an allele frequency of 6.94% in SND cases which was significantly higher compared with normal (0%) and other neurodegenerative disease pathologies (0.74%), suggesting that it is associated with MSA. Our findings indicate that SND and OPCA show distinct early foci of α-syn aggregations, but increasingly converge with longer disease duration to show overlapping patterns of α-syn pathology.
Publisher
Oxford University Press,by American Association of Neuropathologists, Inc
Subject
/ Aged
/ alpha-Synuclein - metabolism
/ Amyloid beta-Peptides - metabolism
/ Atrophy
/ DNA-Binding Proteins - metabolism
/ Female
/ Glucosylceramidase - genetics
/ Humans
/ Male
/ Multiple System Atrophy - complications
/ Multiple System Atrophy - genetics
/ Multiple System Atrophy - metabolism
/ Multiple System Atrophy - pathology
/ Olivopontocerebellar Atrophies - etiology
/ Original
