Document Detail

TDP-43 in ubiquitinated inclusions in the inferior olives in frontotemporal lobar degeneration and in other neurodegenerative diseases: a degenerative process distinct from normal ageing.
MedLine Citation:
PMID:  19330339     Owner:  NLM     Status:  MEDLINE    
Ubiquitin immunoreactive (UBQ-ir) inclusions were present to variable extents in the inferior olivary nucleus (ION) in 37/48 (77%) patients with frontotemporal lobar degeneration (FTLD), in 10/11 (91%) patients with motor neurone disease (MND), in 5/5 (100%) patients with Alzheimer's disease (AD), 5/7 (71%) patients with dementia with Lewy bodies, 13/19 (68%) patients with Parkinson's disease, 11/11(100%) patients with Progressive Supranuclear Palsy, 2/6 (33%) patients with Multisystem Atrophy, 1/3 (33%) patients with Huntington's disease and in 14/14 (100%) normal elderly control subjects. In FTLD, UBQ-ir inclusions were present in 26/32 (81%) patients with FTLD-U, in 10/15 (67%) patients with tauopathy, and in the single patient with Dementia Lacking Distinctive Histology. In 13 FTLD-U patients, and in a single AD and in 2 MND patients, the UBQ-ir inclusions had a rounded, spicular or skein-type appearance, and these were also TDP-43 immunoreactive (TDP-43-ir). In all other affected patients in all diagnostic groups, and in control subjects, the UBQ-ir neuronal cytoplasmic inclusions (NCI) were of a conglomerated type, resembling a cluster of large granules or globules, but were never TDP-43-ir. In 3 of the 13 FTLD-U patients with spicular NCI, conglomerated NCI were also present but in separate cells. Double-labelling immunohistochemistry, and confocal microscopy, for UBQ and TDP-43 confirmed that only the spicular UBQ-ir inclusions in patients with FTLD-U, AD and MND contained TDP-43, though in these patients there were occasional TDP-43 immunoreactive inclusions that were not UBQ-ir. Nuclear TDP-43 immunoreactivity was absent in ION in FTLD-U, AD or MND when TDP-43 cytoplasmic inclusions were present, but remained in neurones with UBQ-ir, TDP-43 negative inclusions. The target protein within the UBQ-ir, TDP-43-negative inclusions remains unknown, but present studies indicate that this is not tau, neurofilament or internexin proteins. These TDP-43 negative, UBQ-ir inclusions appear to be more related to ageing than neurodegeneration, and are without apparent diagnostic significance. The pathophysiological mechanism leading to their formation, and any consequences their presence may have on nerve cell function, remain unknown.
Yvonne Davidson; Hanan Amin; Thomas Kelley; Jing Shi; Jinzhou Tian; Ravindran Kumaran; Tammaryn Lashley; Andrew J Lees; Daniel DuPlessis; David Neary; Julie Snowden; Haruhiko Akiyama; Tetsuaki Arai; Masato Hasegawa; Rina Bandopadhyay; Steve Sikkink; Stuart Pickering-Brown; David M A Mann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-28
Journal Detail:
Title:  Acta neuropathologica     Volume:  118     ISSN:  1432-0533     ISO Abbreviation:  Acta Neuropathol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-07-28     Completed Date:  2009-08-21     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  359-69     Citation Subset:  IM    
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MeSH Terms
Age Factors
Aged, 80 and over
DNA-Binding Proteins / metabolism
Dementia / metabolism,  pathology*
Inclusion Bodies / metabolism,  pathology
Middle Aged
Neurodegenerative Diseases / metabolism,  pathology*
Neurons / metabolism
Olivary Nucleus / metabolism,  pathology
Ubiquitin / metabolism
Ubiquitination / physiology
Grant Support
089701//Wellcome Trust; G-0909//Parkinson's UK; G-7001//Parkinson's UK; G0701441//Medical Research Council
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Ubiquitin; 0/protein TDP-43

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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