CD33 is a transmembrane receptor of the innate immune system that is expressed on the surface of peripheral monocytes and microglial cells in the brain. CD33 was first implicated in Alzheimer’s disease genetics in 2008, and in 2011 reached genome-wide significance in large GWAS in the U.S. and Europe.

2019年5月10日 · The microglial receptor CD33 opposes the effects of TREM2 signaling, and may make a more amenable target because it would be inhibited rather than activated (see Part 5 of this series). In the first phase of the trial, 42 healthy adults will receive a single treatment of either placebo or one of seven different AL003 doses.

2024年4月19日 · One was an antibody, discovered in the blood of cognitively sharp centenarians, that blocks the inhibitory receptor CD33, thus freeing microglia to carry out their protective duties with gusto. Other approaches, including an antibody and small molecule, activated TREM2, promoting microglial phagocytosis and plaque clearance.

CD33, a transmembrane receptor of the innate immune system, is expressed on the surface of microglial cells. Genome-wide association studies (GWAS) have linked variants in CD33 to Alzheimer’s disease risk, and both disease-promoting and protective alleles have been identified. Uniprot lists three isoforms of human CD33. The 364-amino acid ...

2013年8月22日 · Role of CD33 in Alzheimer's Rare variants in the CD33 gene that protect against Alzheimer's disease (right panel) lead to reduced CD33 expression or alter the binding of CD33 to sialic acids. Microglial cells expressing high levels of CD33 are limited in their capacity to internalize and degrade Aβ (left panel).

2022年7月14日 · CD33 is also expressed on peripheral blood monocytes. Findings In March 2019, AL003 entered the clinic with a 54-person trial being run at six sites in the United States and Melbourne, Australia ( May 2019 conference news ).

2022年12月15日 · HEK cells transfected with human CD33 (CD33-3 or CD33m) or mouse (CD33m) isoforms were fixed, permeabilized, then incubated with 24F3 followed by a fluorescently conjugated secondary antibody. Cultures were counterstained with the nuclear stain DAPI (blue). Note 24F3 immunoreactivity (magenta) in the human CD33-transfected cells.

2025年2月22日 · Whitney is a volunteer in the Dominantly Inherited Alzheimer Network (DIAN). Genetic analysis and extensive clinical profiling point toward some possible protective factors, including variants in his CD33 and tau genes, but Llibre-Guerra and colleagues have not pinpointed a reason for his resilience.

2019年7月11日 · CD33-deficient 5xFAD mice had markedly fewer plaques and lower levels of insoluble Aβ42 than 5xFAD controls, but knocking out TREM2 eliminated this protective effect. In fact, TREM2-deficient 5xFAD mice had an increased plaque load compared to regular 5xFAD animals at 8 months of age, as has been reported before ( Feb 2015 news ).

Blots probed with anti-myc antibody 9E10. All three CD33 isoforms are captured by 2C11. *, non-specific bands. [Courtesy of Christian Haass' laboratory.] Generation and epitope mapping. This antibody was generated in rats immunized with a peptide in the C-terminal region of human CD33 that is present in all three isoforms, coupled to ovalbumin.