ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Combined effects of Alzheimer risk variants in the CLU and ApoE genes on ventricular expansion patterns in the elderly.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Analyzing 74,248 Samples Confirms the Association Between CLU rs11136000 Polymorphism and Alzheimer's Disease in Caucasian But Not Chinese population.Scientific reports · 2018Pooled it
- Human IL-34 Deficiency Primes Microglia Toward Alzheimer's Disease-Associated States.medRxiv : the preprint server for health sciences · 2026Article
- Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets.Journal of clinical medicine · 2026Review
- Article
- Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer's disease mice.npj drug discovery · 2025Article
- Genetic biomarkers of cognitive impairment and dementia of potential interest in CKD patients.Journal of nephrology · 2024Review
- Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Can Genetic Markers Predict the Sporadic Form of Alzheimer's Disease? An Updated Review on Genetic Peripheral Markers.International journal of molecular sciences · 2023Review
- Astrocytic response mediated by the CLU risk allele inhibits OPC proliferation and myelination in a human iPSC model.Cell reports · 2023Article
- Large-Scale Integration of Single-Cell RNA-Seq Data Reveals Astrocyte Diversity and Transcriptomic Modules across Six Central Nervous System Disorders.Biomolecules · 2023Article
- Neuronal Hyperactivation in EEG Data during Cognitive Tasks Is Related to the Apolipoprotein J/Clusterin Genotype in Nondemented Adults.International journal of molecular sciences · 2023Article
- Brain structure and allelic associations in Alzheimer's disease.CNS neuroscience & therapeutics · 2023Article
- Emerging Alzheimer's disease therapeutics: promising insights from lipid metabolism and microglia-focused interventions.Frontiers in aging neuroscience · 2023Review
- Clusterin/apolipoprotein J, its isoforms and Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- The impact of Alzheimer's disease susceptibility loci on lateral ventricular surface morphology in older adults.Brain structure & function · 2022Article
- Structural basis of soluble membrane attack complex packaging for clearance.Nature communications · 2021Article
- Neuroimaging PheWAS (Phenome-Wide Association Study): A Free Cloud-Computing Platform for Big-Data, Brain-Wide Imaging Association Studies.Neuroinformatics · 2021Article
- Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer's disease neuropathology.Molecular neurodegeneration · 2021Article
- White Matter Microstructure is Associated with Serum Clusterin and Everyday Functioning in a Sample of Nondemented Older Adults.Current Alzheimer research · 2021Article
- The Down-Regulation of Clusterin Expression Enhances the αSynuclein Aggregation Process.International journal of molecular sciences · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The C allele at the rs11136000 locus in the clusterin (CLU) gene is the third strongest known genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent genome-wide association study of LOAD found the strongest evidence of association with CLU at rs1532278, in high linkage disequilibrium with rs11136000. Brain structure and function are related to the CLU risk alleles, not just in LOAD patients but also in healthy young adults. We tracked the volume of the lateral ventricles across baseline, 1-year, and 2-year follow-up scans in a large sample of elderly human participants (N = 736 at baseline), from the Alzheimer's Disease Neuroimaging Initiative, to determine whether these CLU risk variants predicted longitudinal ventricular expansion. The rs11136000 major C allele-previously linked with reduced CLU expression and with increased risk for dementia-predicted faster expansion, independently of dementia status or ApoE genotype. Further analyses revealed that the CLU and ApoE risk variants had combined effects on both volumetric expansion and lateral ventricle surface morphology. The rs1532278 locus strongly resembles a regulatory element. Its association with ventricular expansion was slightly stronger than that of rs11136000 in our analyses, suggesting that it may be closer to a functional variant. Clusterin affects inflammation, immune responses, and amyloid clearance, which in turn may result in neurodegeneration. Pharmaceutical agents such as valproate, which counteract the effects of genetically determined reduced clusterin expression, may help to achieve neuroprotection and contribute to the prevention of dementia, especially in carriers of these CLU risk variants.
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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.