ArticleNeuron2025
CLU alleviates Alzheimer's disease-relevant processes by modulating astrocyte reactivity and microglia-dependent synaptic density.
Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- 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
- Stage-dependent associations of plasma clusterin with reduced brain volume, tau pathology, and cognitive impairment across the Alzheimer's disease spectrum.Acta neurologica Belgica · 2026Article
- 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
- CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk.Nature communications · 2026Article
- Innate immune signaling and functions in astrocytes.Nature immunology · 2026Review
- A Multi-Context Regulome-Wide Association Atlas for Genetic Studies of Aging Brain Disorders.medRxiv : the preprint server for health sciences · 2026Article
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Differential protein network and biological functions atlas from multi-tissue proteomics in patients with depression.Molecular psychiatry · 2026Article
- Microglial dynamics and ferroptosis induction in human iPSC-derived neuron-astrocyte-microglia tri-cultures.FEBS open bio · 2026Article
- Depletion of microglial compensation in glial network: Disease-associated response dynamics in the revised amyloid hypothesis.Neuroprotection (Chichester, England) · 2026Review
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Are we fully exploiting genetic discoveries to understand and treat Alzheimer's disease?Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Microglia-Astrocyte Cooperation and Peripheral T Cells in Alzheimer's Disease: State-of-the-Art and Treatment Perspectives.International journal of molecular sciences · 2026Review
- Cell type-agnostic transcriptomic signatures enable uniform comparisons of neural maturation.PLoS biology · 2026Article
- Decoding Alzheimer's genetic risk through intercellular communication in the human brain: Lessons from Clusterin.Current opinion in neurobiology · 2026Review
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- Immunometabolic resistors of aging in long-lived golden spiny mice.Science advances · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Association between Alzheimer's disease and MHC-I antigen processing and presentation pathway: a narrative review.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Genetic studies implicate clusterin (CLU) in the pathogenesis of Alzheimer's disease (AD), yet its precise molecular impact remains unclear. Through unbiased proteomic profiling and functional validation in CLU-deficient astrocytes, we identify increased nuclear factor κB (NF-κB)-dependent signaling and complement C3 secretion. Reduction of astrocyte CLU induced microglia-dependent modulation of extracellular apolipoprotein E (APOE) and phosphorylated tau, as well as increased microglial phagocytosis and reduced synapse numbers. By integrating mouse and human cellular models with comprehensive analyses of human plasma and brain tissue, we demonstrate that CLU AD-risk alleles are associated with reduced CLU protein and heightened inflammatory profiles. These findings establish a mechanistic link between AD genetic risk factors, astrocyte reactivity, and microglia-mediated effects on synaptic integrity. Collectively, these results support a model in which CLU upregulation in response to neuropathology is associated with maintenance of cognitive function, while diminished astrocyte CLU levels heighten disease susceptibility.
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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.