Version 1
: Received: 1 July 2024 / Approved: 2 July 2024 / Online: 2 July 2024 (14:49:32 CEST)
How to cite:
Beckers, L.; Rashid, M.; Lee, A. J.; Chatila, Z. K.; Bennett, D. A.; Vardarajan, B. N.; Bradshaw, E. M. CD33 and SHP-1/PTPN6 Interaction in Alzheimer’s Disease. Preprints2024, 2024070168. https://doi.org/10.20944/preprints202407.0168.v1
Beckers, L.; Rashid, M.; Lee, A. J.; Chatila, Z. K.; Bennett, D. A.; Vardarajan, B. N.; Bradshaw, E. M. CD33 and SHP-1/PTPN6 Interaction in Alzheimer’s Disease. Preprints 2024, 2024070168. https://doi.org/10.20944/preprints202407.0168.v1
Beckers, L.; Rashid, M.; Lee, A. J.; Chatila, Z. K.; Bennett, D. A.; Vardarajan, B. N.; Bradshaw, E. M. CD33 and SHP-1/PTPN6 Interaction in Alzheimer’s Disease. Preprints2024, 2024070168. https://doi.org/10.20944/preprints202407.0168.v1
APA Style
Beckers, L., Rashid, M., Lee, A. J., Chatila, Z. K., Bennett, D. A., Vardarajan, B. N., & Bradshaw, E. M. (2024). CD33 and SHP-1/PTPN6 Interaction in Alzheimer’s Disease. Preprints. https://doi.org/10.20944/preprints202407.0168.v1
Chicago/Turabian Style
Beckers, L., Badri N. Vardarajan and Elizabeth M Bradshaw. 2024 "CD33 and SHP-1/PTPN6 Interaction in Alzheimer’s Disease" Preprints. https://doi.org/10.20944/preprints202407.0168.v1
Abstract
Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer’s disease (AD). CD33, an immunomodulatory transmembrane sialic-acid binding protein expressed on myeloid cells, was identified as one such genetic risk factor associated with Alzheimer’s disease. Several studies explored the molecular outcomes of genetic variation at the CD33 locus. It has been determined that the risk variant associated with AD increases the expression of the large isoform of CD33 (CD33M) in innate immune cells and alters its biological functions. CD33 is thought to signal via the interaction of its ITIM domain and the protein tyrosine phosphatase, SHP-1. Here, we utilize different molecular and computational approaches to investigate how AD-associated genetic variation in CD33 affects its interaction with SHP-1 in human microglia and microglia-like cells. Our findings demonstrate a genotype-dependent interaction between CD33 and SHP-1, which may functionally contribute to the AD risk associated with this CD33 variant. We also found that gene-gene interactions impact AD-related traits.
Keywords
Alzheimer’s disease; microglia; CD33; SHP-1
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
