ArticleCommunications biology2022
Importance of CSF-based Aβ clearance with age in humans increases with declining efficacy of blood-brain barrier/proteolytic pathways.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 53 citations in OpenAlex.
- The glymphatic system clears amyloid beta and tau from brain to plasma in humans.Nature communications · 2026Trial
- A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer's Disease.Alzheimer's research & therapy · 2024Trial
- Regional Cerebrospinal Fluid Motility as a Key Determinant of Soluble Amyloid-β Levels and Kinetics.Research square · 2026Article
- Serial failure of the brain clearance continuum in Alzheimer's disease: mechanisms and therapeutic perspectives.Journal of neurology · 2026Review
- Article
- New insight into Alzheimer's disease: small molecule-Aβ in the brain transport and peripheral organ clearance.Frontiers in aging · 2026Review
- Brain and retina in Alzheimer's disease: Pathological intersections and estimates from imaging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Cerebrospinal fluid draining lymphatics in health and disease: advances and controversies.Nature cardiovascular research · 2025Review
- Advancements in Proteolysis Targeting Chimeras for Targeted Therapeutic Strategies in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Early transcriptional and cellular abnormalities in choroid plexus of a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2025Article
- Divergent actions of physiological and pathological amyloid-β on synapses in live human brain slice cultures.Nature communications · 2025Article
- The pathobiology of neurovascular aging.Neuron · 2025Review
- Article
- LRP1 at the crossroads of Aβ clearance and therapeutic targeting in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer's disease: a potential biomarker of early pathology.Fluids and barriers of the CNS · 2024Article
- Pathology of Amyloid-β (Aβ) Peptide Peripheral Clearance in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Ultrasonic cerebrospinal fluid clearance improves outcomes in hemorrhagic brain injury models.bioRxiv : the preprint server for biology · 2024Article
- A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with Early Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2024Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The kinetics of amyloid beta turnover within human brain is still poorly understood. We previously found a dramatic decline in the turnover of Aβ peptides in normal aging. It was not known if brain interstitial fluid/cerebrospinal fluid (ISF/CSF) fluid exchange, CSF turnover, blood-brain barrier function or proteolysis were affected by aging or the presence of β amyloid plaques. Here, we describe a non-steady state physiological model developed to decouple CSF fluid transport from other processes. Kinetic parameters were estimated using: (1) MRI-derived brain volumes, (2) stable isotope labeling kinetics (SILK) of amyloid-β peptide (Aβ), and (3) lumbar CSF Aβ concentration during SILK. Here we show that changes in blood-brain barrier transport and/or proteolysis were largely responsible for the age-related decline in Aβ turnover rates. CSF-based clearance declined modestly in normal aging but became increasingly important due to the slowing of other processes. The magnitude of CSF-based clearance was also lower than that due to blood-brain barrier function plus proteolysis. These results suggest important roles for blood-brain barrier transport and proteolytic degradation of Aβ in the development Alzheimer's Disease in humans.
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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.