Discovery of a Missense Mutation (Q222K) of the APOE Gene from the Australian Imaging, Biomarker and Lifestyle Study

Blaine R Roberts; Scott B Laffoon; Anne M Roberts; Tenielle Porter; Chris Fowler; Colin L Masters; Edward A Dratz; Simon M Laws

doi:10.3233/ADR-220075

Discovery of a Missense Mutation (Q222K) of the APOE Gene from the Australian Imaging, Biomarker and Lifestyle Study

J Alzheimers Dis Rep. 2023 Feb 24;7(1):165-172. doi: 10.3233/ADR-220075. eCollection 2023.

Authors

Blaine R Roberts^{1

2

3}, Scott B Laffoon^{2

3}, Anne M Roberts^{1

2}, Tenielle Porter^{4

5}, Chris Fowler², Colin L Masters², Edward A Dratz³, Simon M Laws^{4

5}

Affiliations

¹ Emory School of Medicine, Department of Biochemistry, Department of Neurology, Atlanta, GA, USA.
² Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
³ Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, USA.
⁴ Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
⁵ Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.

Abstract

After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer's disease (AD). During our investigation to discovery biomarkers in plasma, using 2D gel electrophoresis, we found an individual with and unusual apoE isoelectric point compared to APOE ɛ2, ɛ3, and ɛ4 carriers. Whole exome sequencing of APOE from the donor confirmed a single nucleotide polymorphism (SNP) in exon 4, translating to a rare Q222K missense mutation. The apoE ɛ4 (Q222K) mutation did not form dimers or complexes observed for apoE ɛ2 & ɛ3 proteins.

Keywords: 2D PAGE; APOE; Alzheimer’s disease; biomarkers; mutation; plasma; proteogenomics.