Affiliations: [a] Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA | [b] Centre for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup Drive, Joondalup 6027, WA, Australia | [c] Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Hollywood Private Hospital, Nedlands 6009, WA, Australia | [d] Department of Pharmacology, University of Louisville, Louisville, KY, USA | [e] Core Proteomics Laboratory, University of Louisville, KY, USA
Correspondence:
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Corresponding author: Professor D. Allan Butterfield, Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506 USA. Tel.: +1 859 257 3184; Fax: +1 859 257 5876; E-mail: dabcns@uky.edu.
Abstract: Objective: To identify oxidatively modified proteins in brains of persons with inherited Alzheimer's disease. Methods: Redox proteomics was used to identify oxidatively modified brain proteins in persons with mutations in the genes for presenilin-1 (PS-1). Results: An initial redox proteomics assessment of oxidatively modified proteins from brains of individuals with PS-1 mutations was performed. These PS1 mutations, Q222H and M233T, are completely penetrant causing early-onset familial AD as previously reported in these Australian families. We show that oxidative modifications of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), γ-enolase, actin, and dimethylarginine dimethylaminohydrolase 1 (DMDMAH-1) are present in the brain of familial AD subjects. Conclusions: These initial results suggest that oxidatively modified proteins are important common features in both familial and sporadic AD.
