Lack of TAR-DNA binding protein-43 (TDP-43) pathology in human prion diseases.
OBJECTIVE
TAR-DNA binding protein-43 (TDP-43) is the major ubiquitinated protein in the aggregates in frontotemporal dementia with ubiquitin-positive, tau-negative inclusions and motor neurone disease. Abnormal TDP-43 immunoreactivity has also been described in Alzheimer's disease, Lewy body diseases and Guam parkinsonism-dementia complex. We therefore aimed to determine whether there is TDP-43 pathology in human prion diseases, which are characterised by variable deposition of prion protein (PrP) aggregates in the brain as amyloid plaques or more diffuse deposits.


METHODS
TDP-43, ubiquitin and PrP were analysed by immunohistochemistry and double-labelling immunofluorescence, in sporadic, acquired and inherited forms of human prion disease.


RESULTS
Most PrP plaques contained ubiquitin, while synaptic PrP deposits were not associated with ubiquitin. No abnormal TDP-43 inclusions were identified in any type of prion disease case, and TDP-43 did not co-localize with ubiquitin-positive PrP plaques or with diffuse PrP aggregates.


CONCLUSIONS
These data do not support a role for TDP-43 in prion disease pathogenesis and argue that TDP-43 inclusions define a distinct group of neurodegenerative disorders.
Isaacs
A M
AM
MRC Prion Unit, UCL Institute of Neurology, London, U.K.
Powell
C
C
Webb
T E
TE
Linehan
J M
JM
Collinge
J
J
Brandner
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000145:classification / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology*; D011328:Prions / Q000378:metabolism; D012016:Reference Values; D025801:Ubiquitin / Q000378:metabolism
D004268:DNA-Binding Proteins; D011328:Prions; D025801:Ubiquitin