TDP-43 Deposition in Prospectively Followed, Cognitively Normal Elderly Individuals: A Correlative Study

Persistent Link:
http://hdl.handle.net/10150/281112
Title:
TDP-43 Deposition in Prospectively Followed, Cognitively Normal Elderly Individuals: A Correlative Study
Author:
Arnold, Stacy J.
Affiliation:
The University of Arizona College of Medicine - Phoenix
Issue Date:
Mar-2013
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Collection Information:
This item is part of the College of Medicine - Phoenix Scholarly Projects 2013 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.
Publisher:
The University of Arizona.
Abstract:
TAR DNA-binding protein 43 (TDP-43) has been heavily researched in recent years due to its involvement in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Numerous studies have also sought to investigate the frequency of TDP-43 deposition in other neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, with very few studies focusing on the relationship of TDP-43 to pathological and clinical parameters within cognitively normal subjects. We sought to explore the deposition of TDP-43 and its relation to pathological and clinical parameters in a series of prospectively followed, cognitively normal, elderly individuals whom have come to autopsy. We screened thick, coronal sections of mesial temporal lobe; containing hippocampus and/or amygdalar regions from a series of 110 cognitively normal subjects (age range 71-100 years) using immunohistochemical methods for phosphorylated TDP-43. Consistent with previous results, we found a 36.4% incidence of pathologic TDP-43. Deposition was detected in the form of dendritic neurites, intranuclear inclusions, and perikaryal cytoplasmic neuronal inclusions. With respect to other concomitant pathologies commonly found in elderly individuals, cases with TDP-43 had a greater proportion of cases with argyrophilic grains (ARG) (40% vs. 18.6%). There was not greater prevalence or densities of other concomitant pathologies, including cerebral white matter rarefaction, incidental Lewy bodies, neurofibrillary tangles or amyloid plaques in TDP-43 positive cases. These results indicate deposition of TDP-43 occurs in a substantial subset of cognitively normal elderly subjects and is more common in those with argyrophilic grains.
MeSH Subjects:
Amyotrophic Lateral Sclerosis; protein TDP-43
Description:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
Mentor:
Beach, Thomas, MD, PhD; Dugger, Brittany, PhD

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleTDP-43 Deposition in Prospectively Followed, Cognitively Normal Elderly Individuals: A Correlative Studyen_US
dc.contributor.authorArnold, Stacy J.en_US
dc.contributor.departmentThe University of Arizona College of Medicine - Phoenixen_US
dc.date.issued2013-03-
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.collectioninformationThis item is part of the College of Medicine - Phoenix Scholarly Projects 2013 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.en_US
dc.publisherThe University of Arizona.en_US
dc.description.abstractTAR DNA-binding protein 43 (TDP-43) has been heavily researched in recent years due to its involvement in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Numerous studies have also sought to investigate the frequency of TDP-43 deposition in other neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, with very few studies focusing on the relationship of TDP-43 to pathological and clinical parameters within cognitively normal subjects. We sought to explore the deposition of TDP-43 and its relation to pathological and clinical parameters in a series of prospectively followed, cognitively normal, elderly individuals whom have come to autopsy. We screened thick, coronal sections of mesial temporal lobe; containing hippocampus and/or amygdalar regions from a series of 110 cognitively normal subjects (age range 71-100 years) using immunohistochemical methods for phosphorylated TDP-43. Consistent with previous results, we found a 36.4% incidence of pathologic TDP-43. Deposition was detected in the form of dendritic neurites, intranuclear inclusions, and perikaryal cytoplasmic neuronal inclusions. With respect to other concomitant pathologies commonly found in elderly individuals, cases with TDP-43 had a greater proportion of cases with argyrophilic grains (ARG) (40% vs. 18.6%). There was not greater prevalence or densities of other concomitant pathologies, including cerebral white matter rarefaction, incidental Lewy bodies, neurofibrillary tangles or amyloid plaques in TDP-43 positive cases. These results indicate deposition of TDP-43 occurs in a substantial subset of cognitively normal elderly subjects and is more common in those with argyrophilic grains.en_US
dc.typeThesisen_US
dc.subject.meshAmyotrophic Lateral Sclerosisen_US
dc.subject.meshprotein TDP-43en_US
dc.descriptionA Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.en_US
dc.contributor.mentorBeach, Thomas, MD, PhDen_US
dc.contributor.mentorDugger, Brittany, PhDen_US
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