CD33 and SHP-1/ Interaction in Alzheimer's Disease

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2024 Sep 28

PMID 39336795

Authors

Lien Beckers

Mamunur Rashid

Annie J Lee

Zena K Chatila

Kirstin A Tamucci

Ryan C Talcoff

Jennifer L Hall

David A Bennett

Badri N Vardarajan

Elizabeth M Bradshaw

Affiliations

Soon will be listed here.

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 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 motif 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 variant. We also found that (SHP-1) gene-gene interactions impact AD-related traits, while (SHP-2) interactions do not.

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