Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease:a comparative study of eight disorders

Abstract

Recent research suggests cell-to-cell transfer of pathogenic proteins such as tau and α-synuclein may play a role in neurodegeneration. Pathogenic spread along neural pathways may give rise to specific spatial patterns of the neuronal cytoplasmic inclusions (NCI) characteristic of these disorders. Hence, the spatial patterns of NCI were compared in four tauopathies, viz., Alzheimer's disease, Pick's disease, corticobasal degeneration, and progressive supranuclear palsy, two synucleinopathies, viz., dementia with Lewy bodies and multiple system atrophy, the 'fused in sarcoma' (FUS)-immunoreactive inclusions in neuronal intermediate filament inclusion disease, and the transactive response DNA-binding protein (TDP-43)-immunoreactive inclusions in frontotemporal lobar degeneration, a TDP-43 proteinopathy (FTLD-TDP). Regardless of molecular group or morphology, NCI were most frequently aggregated into clusters, the clusters being regularly distributed parallel to the pia mater. In a significant proportion of regions, the regularly distributed clusters were in the size range 400-800 μm, approximating to the dimension of cell columns associated with the cortico-cortical pathways. The data suggest that cortical NCI in different disorders exhibit a similar spatial pattern in the cortex consistent with pathogenic spread along anatomical pathways. Hence, treatments designed to protect the cortex from neurodegeneration may be applicable across several different disorders. © 2012 Springer-Verlag.

Publication DOI: https://doi.org/10.1007/s00702-012-0838-3
Divisions: College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences > School of Optometry > Optometry & Vision Science Research Group (OVSRG)
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences > Clinical and Systems Neuroscience
Uncontrolled Keywords: cell to cell transfer,FUS proteinopathy,neuronal cytoplasmic inclusions (NCI),spatial patterns,synucleinopathy,tauopathy,TDP-43 proteinopathy,Biological Psychiatry,Neurology,Clinical Neurology,Psychiatry and Mental health
Publication ISSN: 1435-1463
Last Modified: 04 Jan 2024 08:09
Date Deposited: 20 Dec 2012 08:51
Full Text Link: http://www.spri ... 37258r6v40j567/
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2012-12
Authors: Armstrong, Richard A. (ORCID Profile 0000-0002-5046-3199)
Cairns, Nigel J.

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