Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration
Abstract Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter personality and cognition. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for...
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doaj-532330009e8b407c9122b332db9c0d2d2020-11-25T00:35:06ZengBMCActa Neuropathologica Communications2051-59602017-06-015111210.1186/s40478-017-0454-4Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar DegenerationYvonne S. Davidson0Andrew C. Robinson1Louis Flood2Sara Rollinson3Bridget C. Benson4Yasmine T. Asi5Anna Richardson6Matthew Jones7Julie S. Snowden8Stuart Pickering-Brown9Tammaryn Lashley10David M. A. Mann11Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Salford Royal HospitalDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Salford Royal HospitalDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Salford Royal HospitalDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of ManchesterInstitute of Neurology, Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, University College LondonInstitute of Neurology, Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, University College LondonCerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal Hospital, Stott LaneCerebral Function Unit, Greater Manchester Neurosciences Centre, Salford Royal Hospital, Stott LaneDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Salford Royal HospitalDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of ManchesterInstitute of Neurology, Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, University College LondonDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Salford Royal HospitalAbstract Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter personality and cognition. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP E2 was performed on sections of frontal and temporal cortex with hippocampus from 80 patients with FTLD, stratified by pathology into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those with no known mutation, and on 10 healthy controls. Semi-quantitative analysis assessed hnRNP staining in frontal and temporal cortex, and in dentate gyrus (DG) of hippocampus, in the different pathology and genetic groups. We find that hnRNP E2 immunostaining detects the TDP-43 positive dystrophic neurites (DN) within frontal and temporal cortex, and the neuronal cytoplasmic inclusions (NCI) seen in DG granule cells, characteristic of patients with Semantic Dementia (SD) and type C TDP-43 pathology, but did not detect TDP-43 or tau inclusions in any of the other pathological or genetic variants of FTLD. Double immunofluorescence for hnRNP E2 and TDP-43 showed most TDP-43 immunopositive DN to contain hnRNP E2. Present findings indicate an association between TDP-43 and hnRNP E2 which might underlie the pathogenetic mechanism of this form of FTLD.http://link.springer.com/article/10.1186/s40478-017-0454-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yvonne S. Davidson Andrew C. Robinson Louis Flood Sara Rollinson Bridget C. Benson Yasmine T. Asi Anna Richardson Matthew Jones Julie S. Snowden Stuart Pickering-Brown Tammaryn Lashley David M. A. Mann |
spellingShingle |
Yvonne S. Davidson Andrew C. Robinson Louis Flood Sara Rollinson Bridget C. Benson Yasmine T. Asi Anna Richardson Matthew Jones Julie S. Snowden Stuart Pickering-Brown Tammaryn Lashley David M. A. Mann Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration Acta Neuropathologica Communications |
author_facet |
Yvonne S. Davidson Andrew C. Robinson Louis Flood Sara Rollinson Bridget C. Benson Yasmine T. Asi Anna Richardson Matthew Jones Julie S. Snowden Stuart Pickering-Brown Tammaryn Lashley David M. A. Mann |
author_sort |
Yvonne S. Davidson |
title |
Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration |
title_short |
Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration |
title_full |
Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration |
title_fullStr |
Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration |
title_full_unstemmed |
Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration |
title_sort |
heterogeneous ribonuclear protein e2 (hnrnp e2) is associated with tdp-43-immunoreactive neurites in semantic dementia but not with other tdp-43 pathological subtypes of frontotemporal lobar degeneration |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2017-06-01 |
description |
Abstract Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter personality and cognition. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP E2 was performed on sections of frontal and temporal cortex with hippocampus from 80 patients with FTLD, stratified by pathology into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those with no known mutation, and on 10 healthy controls. Semi-quantitative analysis assessed hnRNP staining in frontal and temporal cortex, and in dentate gyrus (DG) of hippocampus, in the different pathology and genetic groups. We find that hnRNP E2 immunostaining detects the TDP-43 positive dystrophic neurites (DN) within frontal and temporal cortex, and the neuronal cytoplasmic inclusions (NCI) seen in DG granule cells, characteristic of patients with Semantic Dementia (SD) and type C TDP-43 pathology, but did not detect TDP-43 or tau inclusions in any of the other pathological or genetic variants of FTLD. Double immunofluorescence for hnRNP E2 and TDP-43 showed most TDP-43 immunopositive DN to contain hnRNP E2. Present findings indicate an association between TDP-43 and hnRNP E2 which might underlie the pathogenetic mechanism of this form of FTLD. |
url |
http://link.springer.com/article/10.1186/s40478-017-0454-4 |
work_keys_str_mv |
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