Linked Life Data

21118398

Source:http://linkedlifedata.com/resource/pubmed/id/21118398

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-5-27
pubmed:abstractText
Frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), frontotemporal lobar degeneration with motor neuron disease/amyotrophic lateral sclerosis (FTLD-MND/ALS) and MND/ALS are thought to represent a clinicopathological spectrum of TDP-43 proteinopathies. The cerebellum has been little studied in these conditions, probably because of the lack of cerebellar signs in most cases. We examined p62 immunohistochemistry on cerebellar sections from 43 TDP-43 proteinopathies (including cases of FTLD-TDP, FTLD-MND/ALS and MND/ALS) together with 72 cases of other neurodegenerative diseases, seven controls and three other disease conditions. In 11 of the TDP-43 proteinopathies (26%) there were numerous p62-positive cerebellar inclusions, predominantly within the granular layer, but also the molecular and Purkinje cell layer. Furthermore, only one of the remaining 82 cases (a familial tauopathy) showed similar p62 positivity. Immunohistochemistry for ubiquitin was positive in the granular layer inclusions. The immunohistochemistry for phosphorylation-independent TDP-43, hyperphosphorylated tau, ?-synuclein, fusion sarcoma protein (FUS), and neurofilament was negative. In only one case (a case of FTLD-TDP) were the inclusions positive for phosphorylation-dependent TDP43 (p-TDP-43). Those TDP-43 proteinopathy cases that showed the cerebellar inclusions also tended to display other common features, such as a notable excess of p62 pathology when compared to TDP-43 pathology, especially within the pyramidal neurones of the hippocampus but also in some cases within the neocortex. The results suggest that p62-positive inclusions within the cerebellum are seen in a proportion of cases across the range of the TDP-43 proteinopathy spectrum and they appear to be relatively specific for this group of diseases. The question as to whether these cerebellar-positive cases represent a distinct subgroup remains to be answered. Furthermore, the relationship of the p62 positivity in the cerebellum to the underlying pathological processes awaits to be established.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1440-1789
pubmed:author
pubmed:copyrightInfo
© 2010 Japanese Society of Neuropathology.
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
239-49
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP-43 proteinopathies but are only rarely additionally immunopositive for phosphorylation-dependent TDP-43.
pubmed:affiliation
Department of Clinical Neuropathology, King's College Hospital, King's College, London, UK. andrewking@nhs.net
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't