ArticleMolecular neurodegeneration2021
The CD33 short isoform is a gain-of-function variant that enhances Aβ
Article in Molecular neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk.Nature communications · 2026Article
- Mechanisms of increased Alzheimer's disease pathology with R47H and R62H TREM2 variants.Acta neuropathologica · 2026Article
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- 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
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- CSF estrogens' relationships to neuroinflammatory markers and brain networks in middle-aged and older black and white women.Journal of neuroinflammation · 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
- Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer's Disease Therapeutics.Biomedicines · 2025Review
- Peripheral Immune Cells Contribute to the Pathogenesis of Alzheimer's Disease.Molecular neurobiology · 2025Article
- CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.Frontiers in cellular neuroscience · 2025Review
- Advancements in Single-Cell RNA Sequencing Research for Neurological Diseases.Molecular neurobiology · 2024Review
- The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer's Disease Etiopathology.Antioxidants (Basel, Switzerland) · 2024Review
- Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer's disease-related amyloidosis.Journal of neurochemistry · 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
- Alzheimer's Disease: Models and Molecular Mechanisms Informing Disease and Treatments.Bioengineering (Basel, Switzerland) · 2024Review
- Roles in Innate Immunity.Advances in neurobiology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCD33 is genetically linked to Alzheimer's disease (AD) susceptibility through differential expression of isoforms in microglia. The role of the human CD33 short isoform (hCD33m), preferentially encoded by an AD-protective CD33 allele (rs12459419T), is unknown. Here, we test whether hCD33m represents a loss-of-function or gain-of-function variant.
methodsWe have developed two models to test the role of hCD33m. The first is a new strain of transgenic mice expressing hCD33m in the microglial cell lineage. The second is U937 cells where the CD33 gene was disrupted by CRISPR/Cas9 and complemented with different variants of hCD33. Primary microglia and U937 cells were tested in phagocytosis assays and single cell RNA sequencing (scRNAseq) was carried out on the primary microglia. Furthermore, a new monoclonal antibody was developed to detect hCD33m more efficiently.
resultsIn both primary microglia and U937 cells, we find that hCD33m enhances phagocytosis. This contrasts with the human CD33 long isoform (hCD33M) that represses phagocytosis, as previously demonstrated. As revealed by scRNAseq, hCD33m
conclusionsThese results provide strong support that hCD33m represents a gain-of-function isoform and offers insight into what it may take to therapeutically capture the AD-protective CD33 allele.
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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 Socratic graph.