ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2017
Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer's disease.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017. 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 108 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.
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
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Impact of Apolipoprotein E4 on blood-brain barrier integrity in target replacement murine models: a systematic review and meta-analysis.Alzheimer's research & therapy · 2026Pooled it
- mTORC2-NaChannels (Austin, Tex.) · 2026Article
- 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
- Autophagy in Alzheimer's Disease: Mechanisms, Clinical Trials, and Horizons.Neuro-degenerative diseases · 2026Review
- Unlocking the aging brain: mTORC1 as a convergent integrator for neurodegeneration and therapeutic intervention.Biogerontology · 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
- 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
- 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
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- APOE4 and sedentary lifestyle synergistically impair neurovascular function in the visual cortex of awake mice.Communications biology · 2025Article
- mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer's disease in an APOE genotype-dependent manner.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Machine Learning-Driven Prediction of Brain Age for Alzheimer's Risk: APOE4 Genotype and Gender Effects.Bioengineering (Basel, Switzerland) · 2024Article
- The Usnic Acid Analogue 4-FPBUA Enhances the Blood-Brain Barrier Function and Induces Autophagy in Alzheimer's Disease Mouse Models.ACS chemical neuroscience · 2024Article
- Evaluating the effect of rapamycin treatment in Alzheimer's disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol.BMC neurology · 2024Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood-brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E ɛ4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E ɛ4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer's disease intervention studies in human subjects.
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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 OpenQuestion graph.