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: Anil Varma V Vatsavayi, Julia Kofler, Mary Ann A Demichele-Sweet, Patrick S Murray, Oscar L Lopez, Robert A Sweet
• Journal: International psychogeriatrics (Int Psychogeriatr) Vol. 26 Issue 6 Pg. 987-94 (Jun 2014) ISSN: 1741-203X [Electronic] England
• PMID: 24588894 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Alzheimer Disease (complications, pathology)
• Brain Chemistry
• DNA-Binding Proteins (analysis)
• Dentate Gyrus (chemistry)
• Female
• Humans
• Male
• Prefrontal Cortex (chemistry)
• Psychotic Disorders (etiology, pathology)