TDP-43 is consistently co-localized with ubiquitinated inclusions in sporadic and Guam amyotrophic lateral sclerosis but not in familial amyotrophic lateral sclerosis with and without SOD1 mutations

Maekawa, Satomi, Leigh, P Nigel, King, Andrew, Jones, Edith, Steele, John C, Bodi, Istvan, Shaw, Christopher E, Hortobagyi, Tibor and Al-Sarraj, Safa (2009) TDP-43 is consistently co-localized with ubiquitinated inclusions in sporadic and Guam amyotrophic lateral sclerosis but not in familial amyotrophic lateral sclerosis with and without SOD1 mutations. Neuropathology : official journal of the Japanese Society of Neuropathology, 29 (6). pp. 672-83. ISSN 1440-1789

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Abstract

The transactive response (TAR) DNA binding protein 43 (TDP-43) has been recently implicated as a major component of ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS, motor neuron disease: MND) and ALS-related disorders. In this study, we examined abnormal TDP-43 pathology in 13 sporadic ALS (SALS), six familial ALS (FALS) with and without Cu/Zn superoxide dismutase (SOD1) mutations (SOD1-FALS and non-SOD1-FALS), Guam ALS, two frontotemporal lobar degeneration with MND/ALS (FTLD-MND/ALS), one FTLD with ubiquitin-only-immunoreactive inclusions (FTLD-U) and two progressive supranuclear palsy (PSP). Sections from the spinal cord were processed for immunohistochemistry using antibodies against TDP-43, ubiquitin, p62, cystatin C, phosphorylated tau protein (P-tau; AT8), alpha-synuclein and phosphorylated neurofilament protein (P-NF). In 12 out of 13 SALS and both Guam ALS cases ubiquitin and p62-immunoreactive (IR) neuronal inclusions co-localized with TDP-43. In three out of four SOD1-FALS and one of two non-SOD1-FALS cases, TDP-43-IR inclusions were absent despite the presence of p62 and/or ubiquitin-IR inclusions. However, a single TDP-43-IR neuronal inclusion co-localized with p62 and ubiquitin in one SOD1-FALS (His48Gln) case. Except for one neuron in a Guam case, all TDP-43-IR neuronal inclusions were negative for P-tau (AT8). TDP-43-IR glial inclusions and neurites were also demonstrated. The TDP-43 is a consistent component of the ubiquitinated inclusions in SALS and Guam ALS, but TDP-43-IR inclusions are absent or scarce in SOD1-FALS

Item Type: Article
Keywords: Amyotrophic lateral sclerosis (ALS); Cu/Zn superoxide dismutase (SOD1); p62; TAR DNA binding protein 43 (TDP-43); ubiquitin
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
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Depositing User: Patricia Butler
Date Deposited: 15 Nov 2012 15:19
Last Modified: 15 Nov 2012 15:19
URI: http://sro.sussex.ac.uk/id/eprint/42505

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