ArticleMolecular neurodegeneration2020
Astrocyte-derived clusterin suppresses amyloid formation in vivo.
Article in Molecular neurodegeneration, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review.Frontiers in cellular neuroscience · 2022Pooled it
- Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis.Scientific data · 2021Pooled it
- Pooled it
- Clusterin is enriched in plaque-associated astrocytes and localizes to synapses in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- A First-In-Class Antibody Enabling Detection of Altered Peripheral Non-Phosphorylated Clusterin With Translational Potential in Dementia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Depletion of microglial compensation in glial network: Disease-associated response dynamics in the revised amyloid hypothesis.Neuroprotection (Chichester, England) · 2026Review
- Decoding Alzheimer's genetic risk through intercellular communication in the human brain: Lessons from Clusterin.Current opinion in neurobiology · 2026Review
- Scalable discovery of spatial multicellular patterns via neighborhood-to-sequence transformation.Communications biology · 2026Article
- De-2-hydroxyisobutyrylation of clusterin modulates neuropathology and memory deficits in an Alzheimer's disease mouse model.Cell communication and signaling : CCS · 2026Article
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- A spatially informed matrix normal model for gene co-expression analysis in spatial transcriptomics studies.Nucleic acids research · 2025Article
- Astrocytes as Therapeutic Targets in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- INPP5D/SHIP1 is a dual regulator of endo-lysosome function and selective phagocytosis in human microglia.bioRxiv : the preprint server for biology · 2025Article
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- Clusterin Regulates the Mechanisms of Neuroinflammation and Neuronal Circuit Impairment in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Exploring the intersection of atherosclerosis and Alzheimer's disease: the role of inflammation and complement activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- The Emerging Role of the Molecular Chaperone Clusterin in Parkinson's Disease.International journal of molecular sciences · 2025Review
- Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAccumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark of Alzheimer's disease (AD). The clusterin (CLU) gene confers a risk for AD and CLU is highly upregulated in AD patients, with the common non-coding, protective CLU variants associated with increased expression. Although there is strong evidence implicating CLU in amyloid metabolism, the exact mechanism underlying the CLU involvement in AD is not fully understood or whether physiologic alterations of CLU levels in the brain would be protective.
resultsWe used a gene delivery approach to overexpress CLU in astrocytes, the major source of CLU expression in the brain. We found that CLU overexpression resulted in a significant reduction of total and fibrillar amyloid in both cortex and hippocampus in the APP/PS1 mouse model of AD amyloidosis. CLU overexpression also ameliorated amyloid-associated neurotoxicity and gliosis. To complement these overexpression studies, we also analyzed the effects of haploinsufficiency of Clu using heterozygous (Clu
conclusionsThus, both physiologic ~ 30% overexpression or ~ 50% reduction in CLU have substantial impacts on amyloid load and associated pathologies. Our results demonstrate that CLU plays a major role in Aβ accumulation in the brain and suggest that efforts aimed at CLU upregulation via pharmacological or gene delivery approaches offer a promising therapeutic strategy to regulate amyloid pathology.
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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.