ArticleBrain : a journal of neurology2021
A delta-secretase-truncated APP fragment activates CEBPB, mediating Alzheimer's disease pathologies.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- Integrating network medicine and foundation models reveals cell-type-specific regulatory alterations in Alzheimer's disease.NAR genomics and bioinformatics · 2026Article
- IL-18 binding protein attenuates neuroinflammation and cognitive decline in Alzheimer's disease.Journal of neuroinflammation · 2026Article
- Alzheimer's disease diagnosis based on gene selection and cross-tissue validation.Frontiers in genetics · 2026Article
- CD34Journal of advanced research · 2025Article
- Chemotherapeutic drug-triggered AEP-cleaved G3BP1 orchestrates stress granules/nucleoli/mitochondria in osteosarcoma.Bone research · 2025Article
- Effective integration of multi-omics with prior knowledge to identify biomarkers via explainable graph neural networks.NPJ systems biology and applications · 2025Article
- Linking dietary patterns to Alzheimer's disease biomarkers with network mathematical modeling could enable new approach methodologies in preventative AD research: a narrative interdisciplinary review.Frontiers in nutrition · 2025Review
- Expression patterns and clinical value of key m6A RNA modification regulators in smoking patients with coronary artery disease.Epigenetics · 2024Article
- A Single-Cell Atlas of the Substantia Nigra Reveals Therapeutic Effects of Icaritin in a Rat Model of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2024Article
- Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer's Disease and Other Tauopathies.Molecular neurobiology · 2024Review
- Asparagine endopeptidase deficiency mitigates radiation-induced brain injury by suppressing microglia-mediated neuronal senescence.iScience · 2024Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.Nature communications · 2024Article
- Discovery of plasma biomarkers related to blood-brain barrier dysregulation in Alzheimer's disease.Frontiers in bioinformatics · 2024Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- AEP-cleaved DDX3X induces alternative RNA splicing events to mediate cancer cell adaptation in harsh microenvironments.The Journal of clinical investigation · 2023Article
- Cholestanol accelerates α-synuclein aggregation and spreading by activating asparagine endopeptidase.JCI insight · 2023Article
- Ferulic Acid Improves Synaptic Plasticity and Cognitive Impairments by Alleviating the PP2B/DARPP-32/PP1 Axis-Mediated STEP Increase and Aβ Burden in Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Whole-exome sequencing detected a novel APP variant in a Han-Chinese family with Alzheimer's disease.Molecular biology reports · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Amyloid-β precursor protein (APP) is sequentially cleaved by secretases and generates amyloid-β, the major components in senile plaques in Alzheimer's disease. APP is upregulated in human Alzheimer's disease brains. However, the molecular mechanism of how APP contributes to Alzheimer's disease pathogenesis remains incompletely understood. Here we show that truncated APP C586-695 fragment generated by δ-secretase directly binds to CCAAT/enhancer-binding protein beta (CEBPB), an inflammatory transcription factor, and enhances its transcriptional activity, escalating Alzheimer's disease-related gene expression and pathogenesis. The APP C586-695 fragment, but not full-length APP, strongly associates with CEBPB and elicits its nuclear translocation and augments the transcriptional activities on APP itself, MAPT (microtubule-associated protein tau), δ-secretase and inflammatory cytokine mRNA expression, finally triggering Alzheimer's disease pathology and cognitive disorder in a viral overexpression mouse model. Blockade of δ-secretase cleavage of APP by mutating the cleavage sites reduces its stimulatory effect on CEBPB, alleviating amyloid pathology and cognitive dysfunctions. Clearance of APP C586-695 from 5xFAD mice by antibody administration mitigates Alzheimer's disease pathologies and restores cognitive functions. Thus, in addition to the sequestration of amyloid-β, APP implicates in Alzheimer's disease pathology by activating CEBPB upon δ-secretase cleavage.
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