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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.

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.

PMID:
24588894
PMCID:
PMC4157359
DOI:
10.1017/S1041610214000246
[PubMed - indexed for MEDLINE]
Free PMC Article
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