title: TDP-43 pathologic lesions and clinical phenotype in frontotemporal lobar degeneration with ubiquitin-positive inclusions.
abstract: 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.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, 2 Gibson, 3400 Spruce St, Philadelphia, PA 19104-4283, USA. mgrossma@mail.med.upenn.edu
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Wood
authors.forename: Peachie
authors.initials: P
authors.lastname: Moore
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: Linda
authors.initials: L
authors.lastname: Kwong
authors.forename: Mark S
authors.initials: MS
authors.lastname: Forman
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clark
authors.forename: Leo F
authors.initials: LF
authors.lastname: McCluskey
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; D025801:Ubiquitin