ArticleMolecular neurodegeneration2021
Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer's disease neuropathology.
Article in Molecular neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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74 citing papers in PubMed, 96 citations in OpenAlex.
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Yin Yang 1 Specifically Supports the Development of Olig2 Positive Cerebellar Astrocytes.Glia · 2026Article
- A consensus atlas of human brain development defines cell type-specific maturation trajectories across the lifespan.bioRxiv : the preprint server for biology · 2026Article
- Astrocyte-driven multicellular mechanisms of CNS repair and cerebroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- TLR7-induced murine inflammation results in a global neuroinflammatory response driving neural circuit-specific transcriptomic changes.Scientific reports · 2026Article
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Decoding Alzheimer's genetic risk through intercellular communication in the human brain: Lessons from Clusterin.Current opinion in neurobiology · 2026Review
- Extracellular Protein Quality Control in Tau Pathology.Molecular neurobiology · 2026Review
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- Clusterin reverses epitheliopathy, reduces inflammation, and restores goblet cells and corneal nerves in a mouse model of autoimmune dry eye.Scientific reports · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Plasma clusterin levels in autism spectrum disorder: bridging biomarkers to social and cognitive dysfunctions.BMC pediatrics · 2026Article
- Astrocytes as Therapeutic Targets in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Parechovirus-3 infection disrupts immunometabolism and leads to glutamate excitotoxicity in neural organoids.Cellular and molecular life sciences : CMLS · 2025Article
- The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway.Immunity · 2025Article
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- Alzheimer's disease protective allele of Clusterin modulates neuronal excitability through lipid-droplet-mediated neuron-glia communication.Molecular neurodegeneration · 2025Article
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- Clusterin Deficiency Promotes Cellular Senescence in Human Astrocytes.Molecular neurobiology · 2025Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGenome-wide association studies have established clusterin (CLU) as a genetic modifier for late-onset Alzheimer's disease (AD). Both protective and risk alleles have been identified which may be associated with its expression levels. However, the physiological function of clusterin in the central nervous system remains largely unknown.
methodsWe examined Clu expression in mouse brains by immunohistochemistry and high-resolution imaging. We performed electrophysiological recordings and morphological analysis of dendritic spines in wild-type and Clu knockout mice. We tested synaptic function of astrocytic Clu using neuron-glia co-cultures and by AAV-mediated astroglial Clu expression in vivo. Finally, we investigated the role of astrocytic Clu on synaptic properties and amyloid pathology in 5xFAD transgenic mouse model of AD.
resultsWe show that astrocyte secreted Clu co-localizes with presynaptic puncta of excitatory neurons. Loss of Clu led to impaired presynaptic function and reduced spine density in vivo. Neurons co-cultured with Clu-overexpressing astrocytes or treated with conditioned media from HEK293 cells transfected with Clu displayed enhanced excitatory neurotransmission. AAV-mediated astroglial Clu expression promoted excitatory neurotransmission in wild-type mice and rescued synaptic deficits in Clu knockout mice. Overexpression of Clu in the astrocytes of 5xFAD mice led to reduced Aβ pathology and fully rescued the synaptic deficits.
conclusionWe identify Clu as an astrocyte-derived synaptogenic and anti-amyloid factor; the combination of these activities may influence the progression of late-onset AD.
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