ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2023
Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- Convergent mitochondrial impairment and apoptosis driven by simultaneous down-regulation of multiple genes at 11p11.2 in Alzheimer's disease.Molecular psychiatry · 2026Article
- Genetic and molecular evidence linking CTSH to Alzheimer's disease pathophysiology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- LongAllele: a joint inference framework for allele-specific analysis on long-read bulk and single-cell RNA sequencing.bioRxiv : the preprint server for biology · 2026Article
- Genetic Architecture of Cognitive Resilience in Alzheimer's Disease: Mechanisms, Pathways, and Therapeutic Implications.Neurology international · 2026Review
- CSF proteomic quantitative trait loci mapping reveals genetic insights into Alzheimer's disease.Molecular neurodegeneration advances · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1.Aging cell · 2025Article
- Mendelian randomization identifies proteins involved in neurodegenerative diseases.Brain : a journal of neurology · 2025Article
- A comprehensive analysis ofIBRO neuroscience reports · 2025Article
- Integrative multi-omics QTL colocalization maps regulatory architecture in aging human brain.medRxiv : the preprint server for health sciences · 2025Article
- Genetic Insights Into the Role of Cathepsins in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis: Evidence From Mendelian Randomization Study.Brain and behavior · 2025Article
- Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.Nature genetics · 2024Article
- Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Broadening Horizons: Exploring the Cathepsin Family as Therapeutic Targets for Alzheimer's Disease.Aging and disease · 2024Review
- Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Blood Cathepsins on the Risk of Alzheimer's Disease and Related Pathological Biomarkers: Results from Observational Cohort and Mendelian Randomization Study.The journal of prevention of Alzheimer's disease · 2024Observational
- The genetic association between bipolar disorder and dementia: a qualitative review.Frontiers in psychiatry · 2024Review
- Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and informs causal proteins for Alzheimer's disease.Research square · 2023Article
- Identification of highly reliable risk genes for Alzheimer's disease through joint-tissue integrative analysis.Frontiers in aging neuroscience · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, which has a high heritability of up to 79%. Exploring the genetic basis is essential for understanding the pathogenic mechanisms underlying AD development. Recent genome-wide association studies (GWASs) reported an AD-associated signal in the Cathepsin H (CTSH) gene in European populations. However, the exact functional/causal variant(s), and the genetic regulating mechanism of CTSH in AD remain to be determined. In this study, we carried out a comprehensive study to characterize the role of CTSH variants in the pathogenesis of AD. We identified rs2289702 in CTSH as the most significant functional variant that is associated with a protective effect against AD. The genetic association between rs2289702 and AD was validated in independent cohorts of the Han Chinese population. The CTSH mRNA expression level was significantly increased in AD patients and AD animal models, and the protective allele T of rs2289702 was associated with a decreased expression level of CTSH through the disruption of the binding affinity of transcription factors. Human microglia cells with CTSH knockout showed a significantly increased phagocytosis of Aβ peptides. Our study identified CTSH as being involved in AD genetic susceptibility and uncovered the genetic regulating mechanism of CTSH in pathogenesis of AD.
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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 Socratic graph.