Send to

Choose Destination
See comment in PubMed Commons below
Int Psychogeriatr. 2014 Jun;26(6):987-94. doi: 10.1017/S1041610214000246. Epub 2014 Mar 4.

TAR DNA-binding protein 43 pathology in Alzheimer's disease with psychosis.

Author information

  • 1Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • 2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • 3Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.



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.


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.


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.


Our findings indicate that there was no association between concomitant TDP-43 pathology in DG or FC and AD+P.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Cambridge University Press Icon for PubMed Central
    Loading ...
    Support Center