ReviewNature reviews. Neurology2021
The case for low-level BACE1 inhibition for the prevention of Alzheimer disease.
Review in Nature reviews. Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 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
83 citing papers in PubMed, 130 citations in OpenAlex.
- Reversibility of cognitive worsening observed with BACE inhibitor umibecestat in the Alzheimer's Prevention Initiative (API) Generation Studies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Trial
- Targeting the BACE1-GSK-3β Signaling Axis in Alzheimer's Disease: From Molecular Crosstalk to Nanotechnology-Based Translational Strategies.Molecular neurobiology · 2026Review
- Plant Polysaccharides in Alzheimer's Disease: From Phytochemistry to Microbiota-Gut-Brain Axis Mechanisms-Resolving the Pharmacokinetic-Pharmacodynamic Paradox.Molecules (Basel, Switzerland) · 2026Review
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Repurposing FDA-approved drugs as multi-target neuroprotective agents for Alzheimer's disease via computational screening and experimental validation.Scientific reports · 2026Article
- Dietary Bioactives in Alzheimer's Disease: A Critical Appraisal of Clinical Trials and Future Nutritional Strategies.Nutrients · 2026Review
- Ferroptosis and Alzheimer's disease: a new insight into neurodegeneration.Frontiers in immunology · 2026Review
- BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.EMBO reports · 2026Article
- Elenbecestat and Compound 89 Potently Inhibit BACE1 but Not BACE2 When Subchronically Dosed in Non-Human Primates.Proteomics · 2026Article
- Article
- Cerebrovascular protective functions of amyloid precursor protein: Progress and therapeutic prospects.Pharmacology & therapeutics · 2025Review
- BACE1 Expression Is Required for Proper Synaptic Vesicle Dynamics in the Hippocampus.Journal of neurochemistry · 2025Article
- Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Targeted delivery of BACE1 siRNA for synergistic treatment of Alzheimer's disease.Translational neurodegeneration · 2025Article
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
- AI-guided patient stratification improves outcomes and efficiency in the AMARANTH Alzheimer's Disease clinical trial.Nature communications · 2025Article
- Gnb5 is a negative regulator of the BACE1-mediated Aβ generation and ameliorates cognitive deficits in a mouse model of Alzheimer's disease.PLoS biology · 2025Article
- Pleiotropic and sex-specific genetic mechanisms of circulating metabolic markers.Nature communications · 2025Article
- Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer's disease.Science advances · 2025Article
- Tripeptides inhibit dual targets AChE and BACE-1: a computational study.RSC advances · 2025Article
23 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
14 authors at 10 institutions in 5 countries.
Funding
Abstract
Alzheimer disease (AD) is the most common cause of dementia in older individuals (>65 years) and has a long presymptomatic phase. Preventive therapies for AD are not yet available, and potential disease-modifying therapies targeting amyloid-β plaques in symptomatic stages of AD have only just been approved in the United States. Small-molecule inhibitors of β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; also known as β-secretase 1) reduce the production of amyloid-β peptide and are among the most advanced drug candidates for AD. However, to date all phase II and phase III clinical trials of BACE inhibitors were either concluded without benefit or discontinued owing to futility or the occurrence of adverse effects. Adverse effects included early, mild cognitive impairment that was associated with all but one inhibitor; preliminary results suggest that the cognitive effects are non-progressive and reversible. These discontinuations have raised questions regarding the suitability of BACE1 as a drug target for AD. In this Perspective, we discuss the status of BACE inhibitors and suggest ways in which the results of the discontinued trials can inform the development of future clinical trials of BACE inhibitors and related secretase modulators as preventative therapies. We also propose a series of experiments that should be performed to inform 'go-no-go' decisions in future trials with BACE inhibitors and consider the possibility that low levels of BACE1 inhibition could avoid adverse effects while achieving efficacy for AD prevention.
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What Socratic 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 Socratic graph.