Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Pathology

Supervisor

Dr. Michael J. Strong

Abstract

Amyotrophic lateral sclerosis [ALS] is a neurological disease characterized by the selective loss of motor neurons [MNs] and death due to respiratory failure usually occurs within 3-5 years of symptom onset. Mutations in the genes encoding TAR DNA binding protein of 43 kDa [TDP-43], fused in sarcoma/translocated in liposarcoma [FUS/TLS] and Cu/Zn superoxide dismutase [SOD1] have all been associated with ALS. Never before has a link been made between the variant of ALS and intraneuronal pathology. This thesis has sought to (1) analyze the immunohistochemical expression of TDP-43, FUS/TLS, SOD1, Rho Guanine nucleotide exchange factor [RGNEF], and 5 other ALS-associated proteins across multiple variants of ALS, and (2) characterize the immunohistochemical expression of RGNEF for the first time. Here, I show that mutant SOD1-ALS is a pathologically unique variant of ALS. This finding may be used in the identification of novel families that may be at risk for developing ALS.

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