ArticleCommunications medicine2025
Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial.
Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04200911 (Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway), which is not on this map. Cited by 26 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.
Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway (CARPE DIEM)
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The dual role of mTOR in multiple sclerosis pathophysiology: a systematic review.Journal of neurology · 2026Pooled it
- Lights for aging: Can photobiomodulation restore functionality in the cerebral networks of aged individuals?Neural regeneration research · 2026Article
- The TRAF6-Akt axis is required for efficient lytic replication of KSHV.PLoS pathogens · 2026Article
- Article
- Pharmacological evolution of natural product-based and chemically engineered autophagy-modulating strategies in neurodegenerative diseases: a bibliometric mapping analysis (2006-2025).Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.STAR protocols · 2026Review
- Autophagy in Alzheimer's Disease: Mechanisms, Clinical Trials, and Horizons.Neuro-degenerative diseases · 2026Review
- Rewiring mTOR signaling in Alzheimer's disease: emerging mTOR modulators beyond oncology.Bioscience reports · 2026Review
- Putatively Identified Sarmentoside-B Removes Oligomerized Amyloid Peptide from Neurons by Inhibiting mTOR and Restoring Lysosomal Function, in In Vitro Alzheimer's Disease Model.Pharmaceutics · 2026Article
- Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease.GeroScience · 2026Article
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Trends and Research Frontiers in Mammalian Target of Rapamycin and Alzheimer's Disease.Molecular neurobiology · 2026Review
- Autophagy-NLRP3 Inflammasome Crosstalk in Microglia: A Therapeutic Target for Multiple Sclerosis.Inflammation · 2026Review
- Mitochondrial ecosystem restoration in Alzheimer's disease: from mechanisms to multi-target therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- Treg-microglia crosstalk in Alzheimer's disease: stage-dependent dynamics, molecular mechanisms, and translational challenge.Frontiers in aging neuroscience · 2026Review
- Decoding Vascular Senescence: Cellular Insights and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Calibrating microglia states in Alzheimer's disease: decoding immune-metabolic networks and nano-targeted multicomponent therapies.Frontiers in immunology · 2026Review
- Senolytics as Modulators of Critical Signaling Pathways: a Promising Strategy to Combat Brain Aging and Neurodegenerative Disorders.Molecular neurobiology · 2025Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
backgroundRapamycin has been shown to extend lifespan and acts on pathologies underlying Alzheimer's disease and related dementias in animal models. However, rapamycin's clinical application remains underexplored.
methodsWe conducted a single-site open-label phase 1 clinical trial (ClinicalTrials.gov: NCT04200911) to examine the effects of rapamycin in humans. Eligible participants were people 55-85 years old with mild cognitive impairment or early-stage dementia, which was defined as having a Global Clinical Dementia Rating Scale Score of 0.5-1. All participants received rapamycin (1 mg/day) for eight weeks. The primary aim was to evaluate rapamycin's central nervous system penetrance by assaying drug levels in the cerebrospinal fluid (CSF) before and after treatment. Secondary aims evaluated safety, cognition, Alzheimer's disease, and inflammatory biomarkers in the CSF and plasma.
resultsIn ten participants (mean age 74 ± 4 years, 60% female), we find that rapamycin is not detectable in the CSF before or after treatment. After treatment, we find that twenty, mostly mild adverse events occur, systolic blood pressure and hemoglobin A1c increase, multiple erythrocyte parameters decrease, and there are no significant cognitive changes. Furthermore, we find that CSF phosphorylated tau-181 (mean change (95% confidence interval) pg/ml), 2.64 [0.70-4.59]), glial fibrillary acidic protein (6262.21 [3787.44-9373.84]), and neurofilament light (367.19 [204.28-561.61]) and plasma interferon gamma (4.37 [3.01-5.74]), interleukin 5 (0.33 [0.12-0.64]), vascular endothelial growth factor D (3741.03 [1505.98-5976.07]), soluble fms-like tyrosine kinase-1 (258.88 [89.03-428.74]) and placental growth factor (20.81 [12.38-29.25]) significantly increase (FDR-corrected p-value < 0.05).
conclusionsRapamycin is not detectable in the CSF before or after treatment, but several Alzheimer's disease and inflammatory biomarkers increase after treatment. Our results highlight the need to better understand the biological effects and clinical impact of repurposing rapamycin for Alzheimer's disease.
Identifiers
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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 Socratic graph.