ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Inpp5d haplodeficiency alleviates tau pathology in the PS19 mouse model of Tauopathy.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain.Science advances · 2026Article
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- 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
- Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.bioRxiv : the preprint server for biology · 2026Article
- Clearing truncated tau protein restores neuronal function and prevents microglia activation in tauopathy mice.Cell reports · 2025Article
- Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1.Aging cell · 2025Article
- PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- Inpp5d haplodeficiency alleviates tau pathology in the PS19 mouse model of Tauopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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11 authors.
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Abstract
introductionA noncoding variant (rs35349669) within INPP5D, a lipid and protein phosphatase restricted to microglia in the brain, is linked to increased susceptibility to Alzheimer's disease (AD). While Inpp5d is well-studied in amyloid pathology, its role in tau pathology remains unclear.
methodsPS19 Tauopathy mice were crossed with Inpp5d-haplodeficient (Inpp5d+/-) mice to examine the impact of Inpp5d in tau pathology.
resultsIncreased INPP5D expression correlated positively with phospho-Tau AT8 in PS19 mice. Inpp5d haplodeficiency mitigated hyperphosphorylated tau levels (AT8, AT180, AT100, and PHF1) and motor deficits in PS19 mice. Transcriptomic analysis revealed an up-regulation of genes associated with immune response and cell migration. DISCUSSION: Our findings define an association between INPP5D expression and tau pathology in PS19 mice. Alleviation in hyperphosphorylated tau, motor deficits, and transcriptomics changes in haplodeficient-Inpp5d PS19 mice indicate that modulation in INPP5D expression may provide therapeutic potential for mitigating tau pathology and improving motor deficits. HIGHLIGHTS: The impact of Inpp5d in the context of tau pathology was studied in the PS19 mouse model. INPP5D expression is associated with tau pathology. Reduced Inpp5d expression in PS19 mice improved motor functions and decreased total and phospho-Tau levels. Inpp5d haplodeficiency in PS19 mice modulates gene expression patterns linked to immune response and cell migration. These data suggest that inhibition of Inpp5d may be a therapeutic approach in tauopathies.
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