ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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37 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- The complement cascade in Alzheimer's disease: a systematic review and meta-analysis.Molecular psychiatry · 2021Pooled it
- Convergent mitochondrial impairment and apoptosis driven by simultaneous down-regulation of multiple genes at 11p11.2 in Alzheimer's disease.Molecular psychiatry · 2026Article
- Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Hallmarks of aging in age-related macular degeneration and age-related neurological disorders: novel insights into common mechanisms and clinical relevance.Eye (London, England) · 2025Review
- Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality.Journal of neural engineering · 2024Article
- Factor H's Control of Complement Activation Emerges as a Significant and Promising Therapeutic Target for Alzheimer's Disease Treatment.International journal of molecular sciences · 2024Article
- Associations of cerebrospinal fluid complement proteins with Alzheimer's pathology, cognition, and brain structure in non-dementia elderly.Alzheimer's research & therapy · 2024Article
- Discovery of plasma biomarkers related to blood-brain barrier dysregulation in Alzheimer's disease.Frontiers in bioinformatics · 2024Article
- Alzheimer's disease-associated complement gene variants influence plasma complement protein levels.Journal of neuroinflammation · 2023Article
- Euphejolkinolide A, a newHeliyon · 2023Article
- Convergent transcriptomic and genomic evidence supporting a dysregulation of CXCL16 and CCL5 in Alzheimer's disease.Alzheimer's research & therapy · 2023Article
- Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H.Frontiers in psychiatry · 2023Article
- Complement component 3 and complement factor H protein levels are altered in brain tissues from people with human immunodeficiency virus: A pilot study.Frontiers in aging neuroscience · 2022Article
- A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline.Signal transduction and targeted therapy · 2021Article
- Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects.International journal of molecular sciences · 2021Article
- The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration.Frontiers in cellular neuroscience · 2021Article
- Complement Activation in the Central Nervous System: A Biophysical Model for Immune Dysregulation in the Disease State.Frontiers in molecular neuroscience · 2021Article
- Neuroprotective effects of verbascoside against Alzheimer's disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice.Journal of neuroinflammation · 2020Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.
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