TDP-43 pathologic lesions and clinical phenotype in frontotemporal lobar degeneration with ubiquitin-positive inclusions.
BACKGROUND
TDP-43 is a major ubiquitinated disease protein in the pathologic condition of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U).


OBJECTIVE
To investigate the demographic, clinical, and neuropsychological features associated with subtypes of FTLD-U with TDP-43 inclusions (FTLD-U/TDP-43).


METHODS
Retrospective clinical-pathologic study.


METHODS
Academic medical center. Patients Twenty-three patients with histopathologically proven FTLD-U.


METHODS
Demographic, symptom, neuropsychological, and autopsy characteristics.


RESULTS
There are notably different clinical and neuropsychological patterns of impairment in FTLD-U subtypes. Patients with FTLD-U/TDP-43 characterized by numerous neuronal intracytoplasmic inclusions have shorter survival; patients with FTLD-U/TDP-43 featuring numerous neurites have difficulty with object naming; and patients with FTLD-U/TDP-43 in whom neuronal intranuclear inclusions are present have substantial executive deficits. There are also different anatomical distributions of ubiquitin pathologic features in FTLD-U subgroups, consistent with their cognitive deficits.


CONCLUSIONS
Distinct TDP-43 profiles may affect clinical phenotypes differentially in patients with FTLD-U.
Grossman
Murray
M
Department of Neurology, University of Pennsylvania School of Medicine, 2 Gibson, 3400 Spruce St, Philadelphia, PA 19104-4283, USA. mgrossma@mail.med.upenn.edu
Wood
Elisabeth M
EM
Moore
Peachie
P
Neumann
Manuela
M
Kwong
Linda
L
Forman
Mark S
MS
Clark
Christopher M
CM
McCluskey
Leo F
LF
Miller
Bruce L
BL
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
D000368:Aged; D001344:Autopsy; D001921:Brain / Q000473:pathology; D003071:Cognition / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D003627:Data Interpretation, Statistical; D003704:Dementia / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010641:Phenotype; D011597:Psychomotor Performance / Q000502:physiology; D012189:Retrospective Studies; D025801:Ubiquitin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D025801:Ubiquitin