ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2013
Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05386914 (Part I), which is not on this map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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.
Part I: Short Term ApoE-dependent Cerebral Blood Flow Response to Sirolimus in Cognitively Normal Adults Part II: Short Term ApoE-dependent Cerebral Blood Flow and Lung Perfusion Response to Sirolimus in Cognitively Normal Adults
Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.
- Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach.Current neuropharmacology · 2019Pooled it
- A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.Experimental gerontology · 2018Trial
- Rapamycin increases cerebral blood flow and modulates metabolic, inflammatory, and microbiome profiles in healthy middle-aged APOE4 carriers: A pilot single-arm trial.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Short-term mTOR inhibition by rapamycin improves cardiac and endothelial function in older men: a proof-of concept pilot study.GeroScience · 2026Article
- Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease.GeroScience · 2026Article
- Regulation of survival, growth, and metabolism by neuronal mTOR.GeroScience · 2026Article
- Study protocol: role of the blood-brain barrier in stress resilience: investigating new pathways towards Pharmacological augmentation of stress resilience (a PHASR-PP project study).BMC psychology · 2026Article
- Rapamycin Reduces Amyloid-β Plaques and Improves Behavioral Performance in a Sex-Dependent Manner in Mouse Models of Amyloidosis.CNS neuroscience & therapeutics · 2026Article
- Cerebellar Abnormalities: A Component of Autism Pathophysiology.Medicina (Kaunas, Lithuania) · 2026Review
- Cell-intrinsic mTOR/LET-363 influences morphological aging of the ALM touch receptor neuron in Caenorhabditis elegans.PloS one · 2026Article
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Targeting Liquid-Liquid Phase Separation and Autophagy in Alzheimer's Disease: Insights into Molecular Mechanisms and Therapeutic Potential.Neurochemical research · 2025Review
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- PF-04691502, a PI3K/mTOR Dual Inhibitor, Ameliorates AD-like Pathology in a Mouse Model of AD.Cells · 2025Article
- Microglial MS4A4A Protects against Epileptic Seizures in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial.Communications medicine · 2025Article
- The Role of Glial Cell Senescence in Alzheimer's Disease.Journal of neurochemistry · 2025Review
89 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
Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias.
Indexed as
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.