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

Published online by Cambridge University Press:  04 March 2014

Anil Varma V. Vatsavayi ,
Julia Kofler ,
Mary Ann A. DeMichele-Sweet ,
Patrick S. Murray ,
Oscar L. Lopez  and
Robert A. Sweet
Anil Varma V. Vatsavayi
Affiliation:
Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA VISN 4 Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
Julia Kofler
Affiliation:
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Mary Ann A. DeMichele-Sweet
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Patrick S. Murray
Affiliation:
Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA VISN 4 Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
Oscar L. Lopez
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Robert A. Sweet*
Affiliation:
Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA VISN 4 Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
*
Correspondence should be addressed to: Dr Robert A. Sweet, Biomedical Science Tower, W1645 3811, O'Hara St. Pittsburgh, PA 15213, USA. Phone: +412-624-0064; Fax: +412-624-9910. Email: sweetra@upmc.edu.
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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.

Keywords

TDP-43Alzheimer's diseasepsychosis
Type
Research Article
Information
International Psychogeriatrics , Volume 26 , Issue 6 , June 2014 , pp. 987 - 994
Copyright
Copyright © International Psychogeriatric Association 2014 

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