ArticleNeurobiology of disease2021
INPP5D expression is associated with risk for Alzheimer's disease and induced by plaque-associated microglia.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- The impact of CSF1R inhibitor-mediated microglial depletion in rodent models of Alzheimer's and Parkinson's disease: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2026Pooled it
- Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer's disease dementia.Communications biology · 2026Article
- The SHIP1-inflammatory-lipid axis in Alzheimer's disease: from genetic risk to spatiotemporal mechanistic insights.Journal of neuroinflammation · 2026Review
- Whole-genome sequencing reveals an East Asian-specific rare variant of INPP5J associated with Alzheimer's disease.Translational psychiatry · 2026Article
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients.Acta neuropathologica communications · 2026Article
- Sex and life experience shape locus coeruleus pretangle tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Single-cell sequencing analysis and machine learning model reveal aberrant TIM-3 expression in microglia during Alzheimer's disease progression.Journal of translational medicine · 2026Article
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Spatial and single-cell transcriptomics reveal the reorganization of cerebellar microglia with aging.Cell reports · 2025Article
- High throughput identification of genetic regulators of microglial inflammatory processes in Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease.Immunity · 2025Article
- Layer-Specific Colocalization of Microglia with Amyloid Plaques in the Middle Temporal Gyrus Predicts Cognitive Decline in Alzheimer's Disease.Aging and disease · 2025Article
- Aminocholestane and Aminoandrostane Inhibitors of the SH2 Domain-Containing Inositol 5'-Phosphatase (SHIP).ChemMedChem · 2025Article
- Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research.Molecular neurodegeneration · 2025Review
- 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
- A unified framework for cell-type-specific eQTL prioritization by integrating bulk and scRNA-seq data.American journal of human genetics · 2025Article
- Functional Characterization of the SHIP1-Domains Regarding Their Contribution to Inositol 5-Phosphatase Activity.Biomolecules · 2025Article
- A subcellular sampling instrument allows spatial resolution of amyloid deposit-derived organelle-specific effects in microglia.Communications biology · 2025Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, robust microgliosis, neuroinflammation, and neuronal loss. Genome-wide association studies recently highlighted a prominent role for microglia in late-onset AD (LOAD). Specifically, inositol polyphosphate-5-phosphatase (INPP5D), also known as SHIP1, is selectively expressed in brain microglia and has been reported to be associated with LOAD. Although INPP5D is likely a crucial player in AD pathophysiology, its role in disease onset and progression remains unclear. We performed differential gene expression analysis to investigate INPP5D expression in AD and its association with plaque density and microglial markers using transcriptomic (RNA-Seq) data from the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) cohort. We also performed quantitative real-time PCR, immunoblotting, and immunofluorescence assays to assess INPP5D expression in the 5xFAD amyloid mouse model. Differential gene expression analysis found that INPP5D expression was upregulated in LOAD and positively correlated with amyloid plaque density. In addition, in 5xFAD mice, Inpp5d expression increased as the disease progressed, and selectively in plaque-associated microglia. Increased Inpp5d expression levels in 5xFAD mice were abolished entirely by depleting microglia with the colony-stimulating factor receptor-1 antagonist PLX5622. Our findings show that INPP5D expression increases as AD progresses, predominantly in plaque-associated microglia. Importantly, we provide the first evidence that increased INPP5D expression might be a risk factor in AD, highlighting INPP5D as a potential therapeutic target. Moreover, we have shown that the 5xFAD mouse model is appropriate for studying INPP5D in AD.
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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.