Back to Search
Start Over
Spread of pathology in amyotrophic lateral sclerosis: assessment of phosphorylated TDP-43 along axonal pathways.
Spread of pathology in amyotrophic lateral sclerosis: assessment of phosphorylated TDP-43 along axonal pathways.
- Source :
-
Acta neuropathologica communications [Acta Neuropathol Commun] 2015 Jul 28; Vol. 3, pp. 47. Date of Electronic Publication: 2015 Jul 28. - Publication Year :
- 2015
-
Abstract
- Introduction: The progression of amyotrophic lateral sclerosis (ALS) through the brain has recently been staged using independent neuropathological and neuroimaging modalities. The two schemes tie into the concept of pathological spread through corticofugal axonal transmission that stems from observation of oligodendrocyte pTDP-43 aggregates along with neuronal inclusions. Here, we aimed to assess evidence of transmission along axonal pathways by looking for pTDP-43 oligodendrocyte pathology in involved white matter tracts, and to present a first validation of the neuropathological staging scheme. pTDP-43 immunohistochemistry was performed in select white matter tracts and grey matter regions from the staging scheme in postmortem-confirmed ALS cases (Nā=ā34). Double-labelling immunofluorescence was performed to confirm co-localisation of pTDP-43 immunoreactivity to oligodendrocytes.<br />Results: While pTDP-43 immunoreactive oligodendrocytes were frequent in the white matter under the motor and sensory cortices, similar assessment of the white matter along the corticospinal tract and in the corpus callosum and cingulum bundle of the same cases revealed no pTDP-43 pathology, questioning the involvement of oligodendrocytes in pathological propagation. The assessment of Betz cell loss revealed that the lack of deep white matter pTDP-43 oligodendrocyte pathology was not due to an absence of motor axons. Assessment of the propagation of pathology to different grey matter regions validated that all cases could be allocated to one of four neuropathological stages, although Stage 4 cases were found to differ significantly in age of onset (~10 years older) and disease duration (shorter duration than Stage 3 and similar to Stage 2).<br />Conclusions: Four stages of ALS neuropathology can be consistently identified, although evidence of sequential clinical progression requires further assessment. As limited pTDP-43 oligodendrocyte pathology in deep corticospinal and other white matter tracts from the motor cortex was observed, the propagation of pathology between neurons may not involve oligodendrocytes and the interpretation of the changes observed on neuroimaging should be modified accordingly.
- Subjects :
- Aged
Aged, 80 and over
Chi-Square Distribution
Female
Gray Matter metabolism
Gray Matter pathology
Humans
Male
Middle Aged
Nerve Tissue Proteins metabolism
Statistics, Nonparametric
Amyotrophic Lateral Sclerosis pathology
Axons metabolism
Brain metabolism
Brain pathology
DNA-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2051-5960
- Volume :
- 3
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica communications
- Publication Type :
- Academic Journal
- Accession number :
- 26216351
- Full Text :
- https://doi.org/10.1186/s40478-015-0226-y