ArticleMolecular psychiatry2021
The acute phase protein lactoferrin is a key feature of Alzheimer's disease and predictor of Aβ burden through induction of APP amyloidogenic processing.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- The cytokines interleukin-6 and interferon-α induce distinct microglia phenotypes.Journal of neuroinflammation · 2022Pooled it
- Lactoferrin Levels in Cerebrospinal Fluid Exhibit Differential Associations with Alzheimer's Disease.Research square · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Clinical translation of salivary MicroAge for understanding the oral-systemic connection in healthy longevity.Frontiers in microbiology · 2026Review
- Ferroptosis and Alzheimer's disease: a new insight into neurodegeneration.Frontiers in immunology · 2026Review
- The Oral-Brain Axis in Alzheimer's Disease: From Microbial Dysbiosis to Neurodegeneration.Microorganisms · 2025Review
- ADAMTS2: More than a procollagen N-proteinase.Genes & diseases · 2025Review
- Lactoferrin levels in cerebrospinal fluid exhibits isoform-specific associations with Alzheimer's disease.medRxiv : the preprint server for health sciences · 2025Article
- Effective integration of multi-omics with prior knowledge to identify biomarkers via explainable graph neural networks.NPJ systems biology and applications · 2025Article
- Lactoferrin as a Candidate Multifunctional Therapeutic in Synucleinopathies.Brain sciences · 2025Review
- Liposomal Lactoferrin Reduces Brain Neuroinflammation in Rats and Alleviates Jetlag and Improves Sleep Quality After Long-Haul Travel.NeuroSci · 2025Article
- An Update of Salivary Biomarkers for the Diagnosis of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- The Association of Serum Lactoferrin Level with Psychological Symptoms, Cognition, and Executive Function in Schizophrenia Patients.Iranian journal of psychiatry · 2025Article
- A Map of Transcriptomic Signatures of Different Brain Areas in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Identification and immunological characterization of genes associated with ferroptosis in Alzheimer's disease and experimental demonstration.Molecular medicine reports · 2024Article
- Brain Iron Dyshomeostasis and Ferroptosis in Alzheimer's Disease Pathophysiology: Two Faces of the Same Coin.Aging and disease · 2024Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- MAD-microbial (origin of) Alzheimer's disease hypothesis: from infection and the antimicrobial response to disruption of key copper-based systems.Frontiers in neuroscience · 2024Review
- Review
- Inflammatory Processes in Alzheimer's Disease-Pathomechanism, Diagnosis and Treatment: A Review.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Amyloidogenic processing of the amyloid precursor protein (APP) forms the amyloid-β peptide (Aβ) component of pathognomonic extracellular plaques of AD. Additional early cortical changes in AD include neuroinflammation and elevated iron levels. Activation of the innate immune system in the brain is a neuroprotective response to infection; however, persistent neuroinflammation is linked to AD neuropathology by uncertain mechanisms. Non-parametric machine learning analysis on transcriptomic data from a large neuropathologically characterised patient cohort revealed the acute phase protein lactoferrin (Lf) as the key predictor of amyloid pathology. In vitro studies showed that an interaction between APP and the iron-bound form of Lf secreted from activated microglia diverted neuronal APP endocytosis from the canonical clathrin-dependent pathway to one requiring ADP ribosylation factor 6 trafficking. By rerouting APP recycling to the Rab11-positive compartment for amyloidogenic processing, Lf dramatically increased neuronal Aβ production. Lf emerges as a novel pharmacological target for AD that not only modulates APP processing but provides a link between Aβ production, neuroinflammation and iron dysregulation.
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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.