SynthesisAlzheimer's research & therapy2024
Utilization of fluid-based biomarkers as endpoints in disease-modifying clinical trials for Alzheimer's disease: a systematic review.
Synthesis in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 16 citations in OpenAlex.
- Brain Health Research in PubMed/MEDLINE: A Bibliometric Analysis of Thematic Structure and Health-Economic Terminology with a Conceptual Performance-Management Framework.Brain sciences · 2026Review
- Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease Cognitive Impairment: A Narrative Review of Clinical Trials.Health science reports · 2026Article
- Targeting the Complement-Microglia Axis for Neuroprotection in Pediatric Epilepsy.Biomedicines · 2026Review
- Rhizomes as Multi-Target Pharmacological Platforms Against Tauopathy: Neuro-Metabolic Crosstalk, Drug-Likeness, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Reimagining GSK-3β Therapeutics in Alzheimer's Disease: From Inhibition to Activity Normalization and Targeted Degradation.Journal of molecular neuroscience : MN · 2026Review
- Contextualizing Blood-Based Biomarkers for Dementia Globally.Journal of neurochemistry · 2026Review
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Ageing, Neurodegeneration and the Endocannabinoid System.Current topics in behavioral neurosciences · 2026Review
- Anemia, iron deficiency, and blood biomarkers for Alzheimer disease: clinical interpretation and dementia risk stratification.Frontiers in nutrition · 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
- Editorial: Real-World Outcomes of Disease-Modifying Therapies Highlight the Need for Diagnostic Biomarkers in Early Alzheimer's Disease.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Cerebrospinal Fluid Amyloid and Tau Biomarker Changes Across the Alzheimer Disease Clinical Spectrum.JAMA network open · 2025Article
- Physical Activity, Alzheimer Plasma Biomarkers, and Cognition.JAMA network open · 2025Article
- Blood biomarkers as surrogate endpoints in Alzheimer's disease research.Frontiers in aging neuroscience · 2025Article
- Analytical and clinical performance of eight SimoaAlzheimer's research & therapy · 2024Article
- Serial Cerebrospinal Fluid Sampling Reveals Trajectories of Potential Synaptic Biomarkers in Early Stages of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Leveraging recent advances in plasma biomarkers to optimize early proof of concept trials in Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.)Article
- Biomarkers in Alzheimer's disease clinical trials: 2025.Alzheimer's & dementia (New York, N. Y.)Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClinical trials in Alzheimer's disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development.
methodsWe systematically reviewed 272 trials (clinicaltrials.gov) with disease-modifying therapies starting between 01-01-2017 and 01-01-2024 and identified which CSF and/or blood-based biomarker endpoints were used per purpose and trial type.
resultsWe found that 44% (N = 121) of the trials employed fluid-based biomarker endpoints among which the CSF ATN biomarkers (Aβ (42/40), p/tTau) were used most frequently. In blood, inflammatory cytokines, NFL, and pTau were most frequently employed. Blood- and CSF-based biomarkers were used approximately equally. Target engagement biomarkers were used in 26% (N = 72) of the trials, mainly in drugs targeting inflammation and amyloid. Lack of target engagement markers is most prominent in synaptic plasticity/neuroprotection, neurotransmitter receptor, vasculature, epigenetic regulators, proteostasis and, gut-brain axis targeting drugs. Positive biomarker results did not always translate to cognitive effects, most commonly the small significant reductions in CSF tau isoforms that were seen following anti-Tau treatments. On the other hand, the positive anti-amyloid trials results on cognitive function were supported by clear effect in most fluid markers.
conclusionsAs the field moves towards primary prevention, we expect an increase in the use of fluid-based biomarkers to determine disease modification. Use of blood-based biomarkers will rapidly increase, but CSF markers remain important to determine brain-specific treatment effects. With improving techniques, new biomarkers can be found to diversify the possibilities in measuring treatment effects and target engagement. It remains important to interpret biomarker results in the context of the trial and be aware of the performance of the biomarker. Diversifying biomarkers could aid in the development of surrogacy biomarkers for different drug targets.
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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.