Neuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration
| Autor: | Linda K. Kwong, Lior Rennert, Murray Grossman, John Q. Trojanowski, Ahmed Yousef, Matthew D. Byrne, EunRan Suh, Yan Xu, Vivianna M. Van Deerlin, Sharon X. Xie, Virginia M.-Y. Lee, Edward B. Lee, John L. Robinson, David J. Irwin |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pathology TDP-43 lcsh:RC346-429 Pattern Recognition Automated Cohort Studies 0302 clinical medicine Progranulins C9orf72 Image Processing Computer-Assisted Inclusion Bodies Neurons biology Cell Death Neurodegeneration Brain Antigens Nuclear Frontotemporal lobar degeneration Immunohistochemistry DNA-Binding Proteins medicine.anatomical_structure Cerebral cortex Cerebellar cortex Disease Progression Intercellular Signaling Peptides and Proteins Female Algorithms GRN medicine.medical_specialty Nerve Tissue Proteins Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience mental disorders medicine Humans Genetic Predisposition to Disease lcsh:Neurology. Diseases of the nervous system Aged C9orf72 Protein Research nutritional and metabolic diseases medicine.disease nervous system diseases NeuN 030104 developmental biology nervous system biology.protein Neurology (clinical) Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Acta Neuropathologica Communications, Vol 5, Iss 1, Pp 1-15 (2017) Acta Neuropathologica Communications |
| ISSN: | 2051-5960 |
| Popis: | Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We explored if cortical neurons detected by NeuN decreased with increasing TDP-43 inclusion pathology in the postmortem brains of 63 patients with sporadic and familial FTLD-TDP. Semi-automated quantitative algorithms to quantify histology in tissue sections stained with antibodies specific for pathological or phosphorylated TDP-43 (pTDP-43) and NeuN were developed and validated in affected (cerebral cortex) and minimally affected (cerebellar cortex) brain regions of FTLD-TDP cases. Immunohistochemistry (IHC) for NeuN and other neuronal markers found numerous neurons lacking reactivity, suggesting NeuN may reflect neuron health rather than neuron loss in FTLD. We found three patterns of NeuN and pTDP-43 reactivity in our sample of cortical tissue representing three intracortical region-specific stages of FTLD-TDP progression: Group 1 showed low levels of pathological pTDP-43 and high levels NeuN, while Group 2 showed increased levels of pTDP-43, and Group 3 tissues were characterized by reduced staining for both pTDP-43 and NeuN. Comparison of non-C9orf72/GRN FTLD-TDP with cases linked to both GRN mutations and C9orf72 expansions showed a significantly increased frequency of Group 3 histopathology in the latter cases, suggesting more advanced cortical disease. Hence, we propose that IHC profiles of pTDP-43 and NeuN reflect the burden of pTDP-43 and its deleterious effects on neuron health. Electronic supplementary material The online version of this article (10.1186/s40478-017-0471-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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