ArticleMolecular neurodegeneration2024
Alzheimer's disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice.
Article in Molecular neurodegeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- 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
- Targeted cellular micropharmacies deliver therapeutic agents to the brain.EMBO molecular medicine · 2026Article
- SRSF1 as a promising biomarker and key player in the pathogenesis of Alzheimer's disease.Molecular medicine reports · 2026Article
- Abi3Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.Molecular neurobiology · 2026Review
- Targeting microglial C1q alleviates blood-brain barrier disruption in the thalamus after cortical infarction.Journal of neuroinflammation · 2026Article
- Writers and readers of sialylation in immunoregulation in cancer.The Journal of biological chemistry · 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
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and emerging therapeutic targets.Frontiers in cellular neuroscience · 2026Review
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Consideration of sex as a biological variable over the history of the 5xFAD Alzheimer's Disease mouse model.Biology of sex differences · 2025Article
- Human microglia differentially respond to β-amyloid, tau, and combined Alzheimer's disease pathologies in vivo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1.Aging cell · 2025Article
- Coupling relationship between glucose and oxygen metabolisms to serve as an imaging biomarker for Alzheimer's disease.Scientific reports · 2025Article
- Identification of potential therapeutic drug targets for sepsis by combining the human plasma proteome and genome: a Mendelian randomization study.Journal of thoracic disease · 2025Article
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16 authors.
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Abstract
Microglia play diverse pathophysiological roles in Alzheimer's disease (AD), with genetic susceptibility factors skewing microglial cell function to influence AD risk. CD33 is an immunomodulatory receptor associated with AD susceptibility through a single nucleotide polymorphism that modulates mRNA splicing, skewing protein expression from a long protein isoform (CD33M) to a short isoform (CD33m). Understanding how human CD33 isoforms differentially impact microglial cell function in vivo has been challenging due to functional divergence of CD33 between mice and humans. We address this challenge by studying transgenic mice expressing either of the human CD33 isoforms crossed with the 5XFAD mouse model of amyloidosis and find that human CD33 isoforms have opposing effects on the response of microglia to amyloid-β (Aβ) deposition. Mice expressing CD33M have increased Aβ levels, more diffuse plaques, fewer disease-associated microglia, and more dystrophic neurites compared to 5XFAD control mice. Conversely, CD33m promotes plaque compaction and microglia-plaque contacts, and minimizes neuritic plaque pathology, highlighting an AD protective role for this isoform. Protective phenotypes driven by CD33m are detected at an earlier timepoint compared to the more aggressive pathology in CD33M mice that appears at a later timepoint, suggesting that CD33m has a more prominent impact on microglia cell function at earlier stages of disease progression. In addition to divergent roles in modulating phagocytosis, scRNAseq and proteomics analyses demonstrate that CD33m
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