ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
A dramatic increase of C1q protein in the CNS during normal aging.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 3 of them syntheses that pooled it.
What it found
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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
279 citing papers in PubMed, 3 syntheses or guidelines pooled it, 424 citations in OpenAlex.
- C1q as a target molecule to treat human disease: What do mouse studies teach us?Frontiers in immunology · 2022Pooled it
- The complement cascade in Alzheimer's disease: a systematic review and meta-analysis.Molecular psychiatry · 2021Pooled it
- Peripheral complement proteins in schizophrenia: A systematic review and meta-analysis of serological studies.Schizophrenia research · 2020Pooled it
- C3 and CD47 mediate sensory-motor circuit refinement during spinal cord development.The Journal of experimental medicine · 2026Article
- Mechanisms of Brain Aging and Their Links to Alzheimer's and Parkinson's Disease Pathology.International journal of molecular sciences · 2026Review
- Article
- Spatial multi-omics identifies early synaptic pruning and context-specific dopaminergic vulnerability in synucleinopathies.Nature communications · 2026Article
- Article
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- Impact of sex differences on microglial function in Alzheimer's disease.Alzheimer's research & therapy · 2026Review
- C1q-CD44 interactions regulate microglial phagocytosis, proliferation, and migration.Journal of neuroinflammation · 2026Article
- Article
- Downregulation of neuronal DRD2 drives microglia synaptic pruning and results in cognitive deficits by promoting CCL2 release in a rat model of chronic migraine.The journal of headache and pain · 2026Article
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Distinct macrophage uptake of engineered and biological particles driven by host age and sex.Science and technology of advanced materials · 2026Article
- Dysfunction of lipid metabolism and lysosomal capacity: at the core of microglial aging?Frontiers in aging neuroscience · 2026Review
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- The inner fire: the shifting paradigm of complement system in aging.Frontiers in immunology · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Microglial clearance, neuroprotection and cognitive recovery via a novel synthetic sulfolipid in Alzheimer's disease.Journal of neuroinflammation · 2025Article
219 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
The decline of cognitive function has emerged as one of the greatest health threats of old age. Age-related cognitive decline is caused by an impacted neuronal circuitry, yet the molecular mechanisms responsible are unknown. C1q, the initiating protein of the classical complement cascade and powerful effector of the peripheral immune response, mediates synapse elimination in the developing CNS. Here we show that C1q protein levels dramatically increase in the normal aging mouse and human brain, by as much as 300-fold. This increase was predominantly localized in close proximity to synapses and occurred earliest and most dramatically in certain regions of the brain, including some but not all regions known to be selectively vulnerable in neurodegenerative diseases, i.e., the hippocampus, substantia nigra, and piriform cortex. C1q-deficient mice exhibited enhanced synaptic plasticity in the adult and reorganization of the circuitry in the aging hippocampal dentate gyrus. Moreover, aged C1q-deficient mice exhibited significantly less cognitive and memory decline in certain hippocampus-dependent behavior tests compared with their wild-type littermates. Unlike in the developing CNS, the complement cascade effector C3 was only present at very low levels in the adult and aging brain. In addition, the aging-dependent effect of C1q on the hippocampal circuitry was independent of C3 and unaccompanied by detectable synapse loss, providing evidence for a novel, complement- and synapse elimination-independent role for C1q in CNS aging.
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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.