ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023
The Alzheimer's disease risk factor INPP5D restricts neuroprotective microglial responses in amyloid beta-mediated pathology.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- Haplotype-resolved methylomes reveal parent-of-origin DNA methylation imbalance in autism spectrum disorder.Science advances · 2026Article
- Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.Journal of medicinal chemistry · 2026Article
- The SHIP1-inflammatory-lipid axis in Alzheimer's disease: from genetic risk to spatiotemporal mechanistic insights.Journal of neuroinflammation · 2026Review
- Immune involvement in neuropsychiatric disorders: Insights from single-cell transcriptomic studies.Psychiatry and clinical neurosciences · 2026Review
- Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.bioRxiv : the preprint server for biology · 2026Article
- CD22 regulates Aβ clearance in microglia through INPP5D signaling.Frontiers in cellular neuroscience · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- INPP5D/SHIP1 is a dual regulator of endo-lysosome function and selective phagocytosis in human microglia.bioRxiv : the preprint server for biology · 2025Article
- LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer's disease model by reprogramming microglia.Translational psychiatry · 2025Article
- Modular inflammation network discovery from large-scale phenotypic screening in genetically heterogeneous mouse brains.Journal of neuroinflammation · 2025Article
- Mozart's rhythm influence on Alzheimer's disease progression via modulation of pathological damage and cognition.iScience · 2025Article
- Unraveling the complex role of microglia in Alzheimer's disease: amyloid β metabolism and plaque formation.Inflammation and regeneration · 2025Review
- Asrij/OCIAD1 depletion reduces inflammatory microglial activation and ameliorates Aβ pathology in an Alzheimer's disease mouse model.Journal of neuroinflammation · 2025Article
- Review
- Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points.Journal of cell communication and signaling · 2025Article
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- Discovery and evaluation of novel SHIP-1 inhibitors.Bioorganic & medicinal chemistry · 2024Article
- Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer's disease-related amyloidosis.Journal of neurochemistry · 2024Review
- Coupling of Alzheimer's Disease Genetic Risk Factors with Viral Susceptibility and Inflammation.Aging and disease · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
introductionMutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis.
methodsWe generated and investigated 5xFAD Inpp5d
resultsSHIP-1 deletion in microglia led to substantially enhanced recruitment of microglia to Aβ plaques, altered microglial gene expression, and marked improvements in neuronal health. Further, SHIP-1 loss enhanced microglial plaque containment and Aβ engulfment when compared to microglia from Cre-negative 5xFAD Inpp5d DISCUSSION: These results define SHIP-1 as a pivotal regulator of microglial responses during Aβ-driven neurological disease and suggest that targeting SHIP-1 may offer a promising strategy to treat Alzheimer's disease. HIGHLIGHTS: Inpp5d deficiency in microglia increases plaque-associated microglia numbers. Loss of Inpp5d induces activation and phagocytosis transcriptional pathways. Plaque encapsulation and engulfment by microglia are enhanced with Inpp5d deletion. Genetic ablation of Inpp5d protects against plaque-induced neuronal dystrophy.
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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.