ReviewAlzheimer's research & therapy2014
Interpreting Alzheimer's disease clinical trials in light of the effects on amyloid-β.
Review in Alzheimer's research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed.
- 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
- Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- A framework for translating tauopathy therapeutics: Drug discovery to clinical trials.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- The Binding of Different Substrate Molecules at the Docking Site and the Active Site of γ-Secretase Can Trigger Toxic Events in Sporadic and Familial Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Inhibition of gamma-secretase activity without interfering in Notch signalling decreases inflammatory response in patients with cutaneous leishmaniasis.Emerging microbes & infections · 2021Article
- Structural Analysis of the Simultaneous Activation and Inhibition of γ-Secretase Activity in the Development of Drugs for Alzheimer's Disease.Pharmaceutics · 2021Article
- Imaging biomarkers in neurodegeneration: current and future practices.Alzheimer's research & therapy · 2020Review
- Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481.ACS medicinal chemistry letters · 2019Article
- A Proposed Roadmap for Parkinson's Disease Proof of Concept Clinical Trials Investigating Compounds Targeting Alpha-Synuclein.Journal of Parkinson's disease · 2019Article
- Inhibition of γ-Secretase Leads to an Increase in Presenilin-1.Molecular neurobiology · 2018Article
- Pharmacological and Toxicological Properties of the Potent OralThe Journal of pharmacology and experimental therapeutics · 2017Article
- Defective Transcytosis of APP and Lipoproteins in Human iPSC-Derived Neurons with Familial Alzheimer's Disease Mutations.Cell reports · 2016Article
- Robust Translation of γ-Secretase Modulator Pharmacology across Preclinical Species and Human Subjects.The Journal of pharmacology and experimental therapeutics · 2016Article
- Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer's disease.Neuroscience and biobehavioral reviews · 2016Review
- Primary age-related tauopathy and the amyloid cascade hypothesis: the exception that proves the rule?Journal of neurology & neuromedicine · 2016Article
- Re-engineering a neuroprotective, clinical drug as a procognitive agent with high in vivo potency and with GABAA potentiating activity for use in dementia.BMC neuroscience · 2015Article
- Autoregulated paracellular clearance of amyloid-β across the blood-brain barrier.Science advances · 2015Article
- Centrally Delivered BACE1 Inhibitor Activates Microglia, and Reverses Amyloid Pathology and Cognitive Deficit in Aged Tg2576 Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Microglial Aβ receptors in Alzheimer's disease.Cellular and molecular neurobiology · 2015Review
- β-Secretase 1's Targeting Reduces Hyperphosphorilated Tau, Implying Autophagy Actors in 3xTg-AD Mice.Frontiers in cellular neuroscience · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The failure of several potential Alzheimer's disease therapeutics in mid- to late-stage clinical development has provoked significant discussion regarding the validity of the amyloid hypothesis. In this review, we propose a minimum criterion of 25% for amyloid-β (Aβ) lowering to achieve clinically meaningful slowing of disease progression. This criterion is based on genetic, risk factor, clinical and preclinical studies. We then compare this minimum criterion with the degree of Aβ lowering produced by the potential therapies that have failed in clinical trials. If the proposed minimum Aβ lowering criterion is used, then the amyloid hypothesis has yet to be adequately tested in the clinic. Therefore, we believe that the amyloid hypothesis remains valid and remains to be confirmed or refuted in future clinical trials.
Identifiers
What OpenQuestion holds
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.