SynthesisHuman molecular genetics2014
CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer's disease susceptibility.
Synthesis in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
95 citing papers in PubMed, 6 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies.Nature genetics · 2022Pooled it
- Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer's disease risk genes.Nature genetics · 2021Pooled it
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia.Future oncology (London, England) · 2018Pooled it
- Associations Between Genetic Variants in 19p13 and 19q13 Regions and Susceptibility to Alzheimer Disease: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2016Pooled it
- CD33 rs3865444 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese, European, and North American Populations.Molecular neurobiology · 2015Pooled it
- Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.The Journal of clinical investigation · 2024Trial
- 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 and clusterin interact biophysically and genetically to modulate Alzheimer risk.Nature communications · 2026Article
- CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.Molecular neurobiology · 2026Review
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- Toothache and Alzheimer's Disease: A Mendelian Randomization Study of the NAAG-CD33 Neuroimmune Axis.Journal of pain research · 2026Article
- Mapping genetic effects on splicing in ten thousand post-mortem brain samples reveals novel mediators of neurological disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Association of CD33 genetic variants with neurocognitive profiles in chronic viral hepatitis.BJPsych open · 2025Article
- Coupling relationship between glucose and oxygen metabolisms to serve as an imaging biomarker for Alzheimer's disease.Scientific reports · 2025Article
- Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing.Nature genetics · 2025Article
- Small molecules as ligands in the tuning of immune regulatory receptors.Frontiers in immunology · 2025Review
- CD33 and SHP-1/Genes · 2024Article
- TREM2 variants that cause early dementia and increase Alzheimer's disease risk affect gene splicing.Brain : a journal of neurology · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
We previously demonstrated that the Alzheimer's disease (AD) associated risk allele, rs3865444(C), results in a higher surface density of CD33 on monocytes. Here, we find alternative splicing of exon 2 to be the primary mechanism of the genetically driven differential expression of CD33 protein. We report that the risk allele, rs3865444(C), is associated with greater cell surface expression of CD33 in both subjects of European and African-American ancestry and that there is a single haplotype influencing CD33 surface expression. A meta-analysis of the two populations narrowed the number of significant SNPs in high linkage disequilibrium (LD) (r(2) > 0.8) with rs3865444 to just five putative causal variants associated with increased protein expression. Using gene expression data from flow-sorted CD14(+)CD16(-) monocytes from 398 healthy subjects of three populations, we show that the rs3865444(C) risk allele is strongly associated with greater expression of CD33 exon 2 (pMETA = 2.36 × 10(-60)). Western blotting confirms increased protein expression of the full-length CD33 isoform containing exon 2 relative to the rs3865444(C) allele (P < 0.0001). Of the variants in strong LD with rs3865444, rs12459419, which is located in a putative SRSF2 splice site of exon 2, is the most likely candidate to mediate the altered alternative splicing of CD33's Immunoglobulin V-set domain 2 and ultimately influence AD susceptibility.
Indexed as
Identifiers
What OpenQuestion holds
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.