ArticleHuman molecular genetics2015
Genetics of CD33 in Alzheimer's disease and acute myeloid leukemia.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia.Future oncology (London, England) · 2018Pooled it
- Large-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases.American journal of human genetics · 2016Pooled it
- CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children's Oncology Group Trial AAML0531.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Trial
- CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.Molecular neurobiology · 2026Review
- Genetics of PLCG2 expression and splicing relative to Alzheimer's disease risk.Molecular neurodegeneration advances · 2026Article
- Association of CD33 genetic variants with neurocognitive profiles in chronic viral hepatitis.BJPsych open · 2025Article
- Mendelian randomization identifies proteins involved in neurodegenerative diseases.Brain : a journal of neurology · 2025Article
- CD33 and SHP-1/Genes · 2024Article
- CRISPR/Cas9 gene editing clarifies the role of CD33 SNP rs12459419 in gemtuzumab ozogamicin-mediated cytotoxicity.International journal of hematology · 2024Article
- Targeting Microglia in Alzheimer's Disease: Pathogenesis and Potential Therapeutic Strategies.Biomolecules · 2024Review
- HuM195 and its single-chain variable fragment increase Aβ phagocytosis in microglia via elimination of CD33 inhibitory signaling.Molecular psychiatry · 2024Article
- Alzheimer's disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice.Molecular neurodegeneration · 2024Article
- Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases.Frontiers in neurology · 2024Review
- Advances in the Understanding of the Correlation Between Neuroinflammation and Microglia in Alzheimer's Disease.ImmunoTargets and therapy · 2024Review
- Long-read RNA-seq atlas of novel microglia isoforms elucidates disease-associated genetic regulation of splicing.medRxiv : the preprint server for health sciences · 2023Article
- Donor bone marrow-derived macrophage engraftment into the central nervous system of patients following allogeneic transplantation.Blood advances · 2023Article
- siRNA drug delivery across the blood-brain barrier in Alzheimer's disease.Advanced drug delivery reviews · 2023Review
- Expression ofGenes · 2023Article
- Article
- Therapeutics of Alzheimer's Disease: Recent Developments.Antioxidants (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The CD33 single-nucleotide polymorphism (SNP) rs3865444 has been associated with the risk of Alzheimer's disease (AD). Rs3865444 is in linkage disequilibrium with rs12459419 which has been associated with efficacy of an acute myeloid leukemia (AML) chemotherapeutic agent based on a CD33 antibody. We seek to evaluate the extent to which CD33 genetics in AD and AML can inform one another and advance human disease therapy. We have previously shown that these SNPs are associated with skipping of CD33 exon 2 in brain mRNA. Here, we report that these CD33 SNPs are associated with exon 2 skipping in leukocytes from AML patients and with a novel CD33 splice variant that retains CD33 intron 1. Each copy of the minor rs12459419T allele decreases prototypic full-length CD33 expression by ∼ 25% and decreases the AD odds ratio by ∼ 0.10. These results suggest that CD33 antagonists may be useful in reducing AD risk. CD33 inhibitors may include humanized CD33 antibodies such as lintuzumab which was safe but ineffective in AML clinical trials. Here, we report that lintuzumab downregulates cell-surface CD33 by 80% in phorbol-ester differentiated U937 cells, at concentrations as low as 10 ng/ml. Overall, we propose a model wherein a modest effect on RNA splicing is sufficient to mediate the CD33 association with AD risk and suggest the potential for an anti-CD33 antibody as an AD-relevant pharmacologic agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.