title: TAR DNA-binding protein 43 pathology in Alzheimer's disease with psychosis.
abstract: BACKGROUND
  TAR DNA-binding protein 43 (TDP-43) has been identified as a major disease protein in frontotemporal lobar degeneration. More recently, TDP-43 proteinopathy has also been observed in Alzheimer's disease (AD) with a characteristic distribution of TDP-43 predominantly in the mesial temporal lobe, and to a lesser degree in the neocortical areas. AD subjects with psychotic symptoms (AD+P) represent a subgroup characterized by greater impairment of frontal cortex-dependent cognitive functions and more severe frontal cortical neuropathology. The aim of this study is to determine whether there is an association between TDP-43 pathology and AD+P. We hypothesized that TDP-43 pathology would be more frequent in AD+P than in AD without psychosis.
  
  
  METHODS
  We studied the presence and distribution of TDP-43 pathology by immunohistochemistry in the dentate gyrus (DG) and prefrontal cortex (FC) of postmortem brain specimens from 68 subjects with a primary neuropathologic diagnosis of AD as determined by the Neuropathology Core of the University of Pittsburgh Alzheimer's Disease Research Center.
  
  
  RESULTS
  Forty-five (66%) subjects were classified as AD+P. Fourteen (20.6%) subjects had TDP-43 pathology in DG, eight (11.8%) had TDP-43 pathology in FC, and six (8.8%) had TDP-43 pathology in both regions. TDP-43 in DG was not significantly associated with AD+P. However, TDP-43 in FC demonstrated a trend toward reduced likelihood of psychosis (p = 0.068). TDP-43 pathology in DG, but not FC, was significantly associated with greater age at death and longer duration of illness.
  
  
  CONCLUSIONS
  Our findings indicate that there was no association between concomitant TDP-43 pathology in DG or FC and AD+P.
authors.affiliation: Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Anil Varma V
authors.initials: AV
authors.lastname: Vatsavayi
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Kofler
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Mary Ann A
authors.initials: MA
authors.lastname: Demichele-Sweet
authors.affiliation: Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Murray
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D001923:Brain Chemistry; D004268:DNA-Binding Proteins / Q000032:analysis*; D018891:Dentate Gyrus / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D017397:Prefrontal Cortex / Q000737:chemistry; D011618:Psychotic Disorders / Q000209:etiology / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins