Progression of alpha‐synuclein pathology in multiple system atrophy of the cerebellar type. (18th October 2016)

• Record Type: Journal Article
• Authors: Brettschneider, J.; Irwin, D. J.; Boluda, S.; Byrne, M. D.; Fang, L.; Lee, E. B.; Robinson, J. L.; Suh, E.; Van Deerlin, V. M.; Toledo, J. B.; Grossman, M.; Hurtig, H.; Dengler, R.; Petri, S.; Lee, V. M.‐Y.; Trojanowski, J. Q.
• Is Part Of: Neuropathology & applied neurobiology. Volume 43:Number 4(2017)
• Page Start: 315
• Page End: 329
• Publication Date: 2016-10-18
• Subjects: α‐synuclein -- cerebellum -- multiple system atrophy; Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12362
• Languages: English
• ISSNs: 0305-1846

Abstract

Abstract : Aims: The aim of this study was to identify early foci of α‐synuclein (α‐syn pathology) accumulation, subsequent progression and neurodegeneration in multiple system atrophy of the cerebellar type (MSA‐C). Methods: We analysed 70‐μm‐thick sections of 10 cases with MSA‐C and 24 normal controls. Results: MSA‐C cases with the lowest burden of pathology showed α‐syn glial cytoplasmic inclusions (GCIs) in the cerebellum as well as in medullary and pontine cerebellar projections. Cerebellar pathology was highly selective and severely involved subcortical white matter, whereas deep white matter and granular layer were only mildly affected and the molecular layer was spared. Loss of Purkinje cells increased with disease duration and was associated with neuronal and axonal abnormalities. Neocortex, basal ganglia and spinal cord became consecutively involved with the increasing burden of α‐syn pathology, followed by hippocampus, amygdala, and, finally, the visual cortex. GCIs were associated with myelinated axons, and the severity of GCIs correlated with demyelination. Conclusions: Our findings indicate that cerebellar subcortical white matter and cerebellar brainstem projections are likely the earliest foci of α‐syn pathology in MSA‐C, followed by involvement of more widespread regions of the central nervous system and neurodegeneration with disease progression. Abstract : In the cerebellar sub‐type of multiple system atrophy (MSA‐C) glial cytoplasmic inclusions first involve subcortical cerebellar white matter and brainstem cerebellar projections with later involvement of additional brain regions and neurodegeneration. The study contributes to determining whether prion‐like propagation of misfolded proteins along anatomical pathways may be important in MSA.