Biochemical Approaches for Studying the Role of CD33 in Alzheimer’s Disease Susceptibility

• Author / Creator

  Jung, Jaesoo

• Alzheimer’s disease (AD) is a common neurodegenerative dementia, and its pathological hallmarks include amyloid-β plaque and neurofibrillary tangle formation in the brain. Genome-wide association studies (GWAS) revealed that a rare single nucleotide polymorphism (SNP) in CD33 is associated with AD susceptibility. This SNP regulates alternative mRNA splicing to generate long (CD33M) and short (CD33m) protein isoforms. These two CD33 isoforms differ in the presence and absence of the V-set glycan-binding domain. Therefore, as higher expression of CD33M correlates with increased AD risk, there is a correlation between loss of glycan binding and AD susceptibility. As the glycan ligands for CD33M are not well understood, the major objective of this thesis is to develop biochemical tools to study the glycan ligands of CD33. To complement studies on CD33M, a second objective is to develop approaches for better understanding alternative mRNA splicing of CD33.

• Subjects / Keywords

  • CD33
  • Carbohydrate sulfotransferase
  • late-onset Alzheimer's disease
  • Siglec

• Graduation date

  Fall 2023

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-yavy-mr39

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.