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

Richard A. Armstrong*, Nigel J. Cairns

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1551-1560
Number of pages10
JournalJournal of Neural Transmission
Volume119
Issue number12
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Molecular Pathology
Inclusion Bodies
Neurodegenerative Diseases
TDP-43 Proteinopathies
Synucleins
Pia Mater
Pick Disease of the Brain
Frontotemporal Lobar Degeneration
Tauopathies
Progressive Supranuclear Palsy
Multiple System Atrophy
Lewy Body Disease
Neural Pathways
Intermediate Filaments
Cytomegalovirus Infections
DNA-Binding Proteins
Sarcoma
Alzheimer Disease
Research
Proteins

Keywords

  • cell to cell transfer
  • FUS proteinopathy
  • neuronal cytoplasmic inclusions (NCI)
  • spatial patterns
  • synucleinopathy
  • tauopathy
  • TDP-43 proteinopathy

Cite this

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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. {\circledC} 2012 Springer-Verlag.",
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Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease : a comparative study of eight disorders. / Armstrong, Richard A.; Cairns, Nigel J.

In: Journal of Neural Transmission, Vol. 119, No. 12, 12.2012, p. 1551-1560.

Research output: Contribution to journalArticle

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