ArticleActa neuropathologica2023
Physiological β-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Population attributable fractions of a wide range of peripheral diseases for the burden of dementia.Nature human behaviour · 2026Pooled it
- Unraveling the Role of LRP1 in Alzheimer's Disease: A Focus on Aβ Clearance and the Liver-Brain Axis.Journal of molecular neuroscience : MN · 2025Pooled it
- Fecal Aβ and tau aggregates are elevated in cognitive impairment and reveal peripheral proteopathic alterations.Alzheimer's research & therapy · 2026Article
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Hepatic and Brain Spatial Gene Expression Changes in Intragastric Alcohol Fed APP/PS1 Alzheimer's Disease Mouse Model.Research square · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- The liver-brain axis: A multidimensional regulatory network implicated in Alzheimer's disease pathogenesis and clinical implications.Animal models and experimental medicine · 2026Review
- Brain and Liver Dual-Targeting Oridonin Nanoparticles to Enhance Aβ Clearance for Alzheimer's Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Brain-body interactions in systemic diseases: a survey from an imaging perspective.MedScience · 2026Review
- Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies.Molecular neurobiology · 2026Review
- Ozone-induced cognitive deficits are mediated by the liver-brain axis: peripheral complement C3 triggers microglial synaptic phagocytosis.Journal of neuroinflammation · 2026Article
- Reexamining the Role of Amyloid β Clearance from the Brain: Exporting Labile Iron from the Interstitial Fluid Performs a Protective Function.International journal of molecular sciences · 2026Review
- Causes of death after surgery among cancer patients: a population-based cohort study.International journal of surgery (London, England) · 2026Article
- Biliary atresia-related liver fibrosis.Frontiers in cell and developmental biology · 2026Review
- Relationship between the preoperative AST/ALT ratio and postoperative delirium and 3-year mortality in patients undergoing total knee or hip arthroplasty: a prospective cohort study.International journal of surgery (London, England) · 2025Article
- Hepatic function is associated with cognitive function in patients with stable schizophrenia.BMC psychiatry · 2025Article
- Plasma proteomic Alzheimer's risk score: Biological age clock and pseudotime trajectory.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Exploring LRP-1 in the liver-brain axis: implications for Alzheimer's disease.Molecular biology reports · 2025Review
- Genetic Correlations and Causalities between Alzheimer's Disease and 35 Biomarkers in Blood and Urine.Molecular neurobiology · 2025Article
- Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.Molecular neurobiology · 2025Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral amyloid-β (Aβ) accumulation due to impaired Aβ clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aβ is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aβ and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aβ42 and 8.9% of Aβ40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aβ receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aβ levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aβ clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aβ burden and cognitive deficits, while enhancing hepatic Aβ clearance via LRP-1 overexpression attenuated cerebral Aβ deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aβ and regulates brain Aβ levels, suggesting that a decline of hepatic Aβ clearance during aging could be involved in AD development, and hepatic Aβ clearance is a novel therapeutic approach for AD.
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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.