Quantification of Phosphorylated TDP-43 Protein in Concomitant Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Pubblico

Abstract

The appearance of frontotemporal dementia (FTD) in a subset of amyotrophic lateral sclerosis (ALS) patients has prompted researchers to investigate pathological and genetic overlaps between the two diseases. The aim of this study was to determine if there is a link between the pathological burden of pTDP-43 protein and the presence of dementia in ALS patients. Quantitative analysis was performed on cognitively normal ALS patients, ALS patients with dementia, and patients with frontotemporal lobar degeneration (FTLD). Our results show that demented ALS patients tend to have a higher burden of pTDP-43 pathology in the dentate gyrus than do cognitively normal ALS patients. However, in four other regions there was no difference in pTDP-43 pathology between the subject groups. Also, two ALS patients had high levels of pTDP-43 in the dentate gyrus but did not present with FTD symptoms. This provides some insight as to the correlation between this protein and clinical dementia, though the exact relationship is not yet certain.

Table of Contents

1. Abstract 1

2. Introduction 2

3. Materials and Methods 9

4. Results 18

5. Discussion 25

6. Limitations and Future Directions 31

7. Conclusion 32

8. References 34

9. Supplementary Tables & Figures 37

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Health Sciences, Pathology
Parola chiave	FTD FTLD frontotemporal lobar degeneration amyotrophic lateral sclerosis ALS frontotemporal dementia pTDP-43
Committee Chair / Thesis Advisor	Glass, Jonathan D, Emory University
Committee Members	Marsteller, Pat, Emory University Crutcher, Michael D, Emory University

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