ArticleBrain : a journal of neurology2014
Sustained peripheral depletion of amyloid-β with a novel form of neprilysin does not affect central levels of amyloid-β.
Article in Brain : a journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- Research progress on Alzheimer's disease vaccines: from Aβ-targeted approaches to clinical translation.Frontiers in aging · 2026Review
- Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Review
- Low-Density Lipoprotein Receptor-Related Protein 1 as a Potential Therapeutic Target in Alzheimer's Disease.Pharmaceutics · 2024Review
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Review
- Alcohol as a Modifiable Risk Factor for Alzheimer's Disease-Evidence from Experimental Studies.International journal of molecular sciences · 2023Review
- Antibody-Mediated Clearance of Brain Amyloid-β: Mechanisms of Action, Effects of Natural and Monoclonal Anti-Aβ Antibodies, and Downstream Effects.Journal of Alzheimer's disease reports · 2023Review
- Blood-brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2022Article
- The "Cerebrospinal Fluid Sink Therapeutic Strategy" in Alzheimer's Disease-From Theory to Design of Applied Systems.Biomedicines · 2022Review
- Amyloid Beta Dynamics in Biological Fluids-Therapeutic Impact.Journal of clinical medicine · 2021Review
- Activating AhR alleviates cognitive deficits of Alzheimer's disease model mice by upregulating endogenous Aβ catabolic enzyme Neprilysin.Theranostics · 2021Article
- Vaccination against β-Amyloid as a Strategy for the Prevention of Alzheimer's Disease.Biology · 2020Review
- Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer's mouse model.Journal of neuroinflammation · 2020Article
- Nanoliposomes as a Therapeutic Tool for Alzheimer's Disease.Frontiers in synaptic neuroscience · 2020Review
- AMBAR, an Encouraging Alzheimer's Trial That Raises Questions.Frontiers in neurology · 2020Article
- Brain Shuttle Neprilysin reduces central Amyloid-β levels.PloS one · 2020Article
- Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy.British journal of pharmacology · 2019Review
- The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration.Frontiers in immunology · 2019Review
- Recommendations on the Use of Anti-CGRP Monoclonal Antibodies in Children and Adolescents.Headache · 2018Article
- Clearance of Amyloid Beta and Tau in Alzheimer's Disease: from Mechanisms to Therapy.Neurotoxicity research · 2018Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease is characterized by the accumulation of amyloid deposits in the brain and the progressive loss of cognitive functions. Although the precise role of amyloid-β in disease progression remains somewhat controversial, many efforts to halt or reverse disease progression have focussed on reducing its synthesis or enhancing its removal. It is believed that brain and peripheral soluble amyloid-β are in equilibrium and it has previously been hypothesized that a reduction in peripheral amyloid-β can lower brain amyloid-β, thereby reducing formation of plaques predominantly composed of insoluble amyloid-β; the so-called peripheral sink hypothesis. Here we describe the use of an amyloid-β degrading enzyme, the endogenous metallopeptidase neprilysin, which is fused to albumin to extend plasma half-life and has been engineered to confer increased amyloid-β degradation activity. We used this molecule to investigate the effect of degradation of peripheral amyloid-β on amyloid-β levels in the brain and cerebrospinal fluid after repeated intravenous dosing for up to 4 months in Tg2576 transgenic mice, and 1 month in rats and monkeys. This molecule proved highly effective at degradation of amyloid-β in the periphery but did not alter brain or cerebrospinal fluid amyloid-β levels, suggesting that the peripheral sink hypothesis is not valid and is the first time that this has been demonstrated in non-human primates.
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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.