ArticleScience translational medicine2013
Increased in vivo amyloid-β42 production, exchange, and loss in presenilin mutation carriers.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02021682 (CNS and Plasma Amyloid-Beta Kinetics in Alzheimers's Disease; A Blood Isotope Labeled Amyloid-beta Test for Alzheimer's Disease.), which is not on this map. Cited by 140 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.
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.
CNS and Plasma Amyloid-Beta Kinetics in Alzheimers's Disease; A Blood Isotope Labeled Amyloid-beta Test for Alzheimer's Disease.
Who cites it
140 citing papers in PubMed, 1 synthesis or guideline pooled it, 226 citations in OpenAlex.
- Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review.The European journal of neuroscience · 2022Pooled it
- Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease.Acta neuropathologica · 2025Trial
- Longitudinal head-to-head comparison ofEuropean journal of nuclear medicine and molecular imaging · 2023Trial
- The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.EMBO molecular medicine · 2018Trial
- The γ-Secretase Modulator, BMS-932481, Modulates Aβ Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers.The Journal of pharmacology and experimental therapeutics · 2016Trial
- The effect of LCZ696 (sacubitril/valsartan) on amyloid-β concentrations in cerebrospinal fluid in healthy subjects.British journal of clinical pharmacology · 2016Trial
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Regional Cerebrospinal Fluid Motility as a Key Determinant of Soluble Amyloid-β Levels and Kinetics.Research square · 2026Article
- NovelWorld journal of radiology · 2026Article
- Choroid plexus remodeling linked to impaired CSF-mediated clearance and Alzheimer's disease progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Molecular Mechanisms Underlying Alzheimer's Disease Pathogenesis: Comprehensive Overview.International journal of molecular sciences · 2026Review
- Modeling neurovascular dysfunction in Alzheimer's disease using an isogenic brain-chip model.Fluids and barriers of the CNS · 2026Article
- Targeting amyloid-β in Alzheimer's disease: A critical analysis of clinical trials and their implications for drug development.Iranian journal of basic medical sciences · 2026Review
- Advancements in Therapy for Alzheimer's Disease Based on the Cerebral Lymphatic System.Degenerative neurological and neuromuscular disease · 2026Article
- Meningeal lymphatics as a therapeutic target for neurodegenerative disorders.Translational neurodegeneration · 2025Review
- Mind over microplastics - what we still don't know.Nature reviews. Neurology · 2025Article
- Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer's disease through disrupted regulated intramembrane proteolysis.Molecular neurodegeneration · 2025Article
- The genetics of neurodegenerative diseases is the genetics of age-related damage clearance failure.Molecular psychiatry · 2025Review
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Aquaporin 4 modulation drives amyloid burden and cognitive abilities in an APPPS1 mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
80 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
15 authors at 3 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is hypothesized to be caused by an overproduction or reduced clearance of amyloid-β (Aβ) peptide. Autosomal dominant AD (ADAD) caused by mutations in the presenilin (PSEN) gene have been postulated to result from increased production of Aβ42 compared to Aβ40 in the central nervous system (CNS). This has been demonstrated in rodent models of ADAD but not in human mutation carriers. We used compartmental modeling of stable isotope labeling kinetic (SILK) studies in human carriers of PSEN mutations and related noncarriers to evaluate the pathophysiological effects of PSEN1 and PSEN2 mutations on the production and turnover of Aβ isoforms. We compared these findings by mutation status and amount of fibrillar amyloid deposition as measured by positron emission tomography (PET) using the amyloid tracer Pittsburgh compound B (PIB). CNS Aβ42 to Aβ40 production rates were 24% higher in mutation carriers compared to noncarriers, and this was independent of fibrillar amyloid deposits quantified by PET PIB imaging. The fractional turnover rate of soluble Aβ42 relative to Aβ40 was 65% faster in mutation carriers and correlated with amyloid deposition, consistent with increased deposition of Aβ42 into plaques, leading to reduced recovery of Aβ42 in cerebrospinal fluid (CSF). Reversible exchange of Aβ42 peptides with preexisting unlabeled peptide was observed in the presence of plaques. These findings support the hypothesis that Aβ42 is overproduced in the CNS of humans with PSEN mutations that cause AD, and demonstrate that soluble Aβ42 turnover and exchange processes are altered in the presence of amyloid plaques, causing a reduction in Aβ42 concentrations in the CSF.
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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.