ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
mTOR Attenuation with Rapamycin Reverses Neurovascular Uncoupling and Memory Deficits in Mice Modeling Alzheimer's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 57 citations in OpenAlex.
- Unlocking the aging brain: mTORC1 as a convergent integrator for neurodegeneration and therapeutic intervention.Biogerontology · 2026Review
- Regulation of survival, growth, and metabolism by neuronal mTOR.GeroScience · 2026Article
- Restriction of Individual Branched-Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rapamycin Reduces Amyloid-β Plaques and Improves Behavioral Performance in a Sex-Dependent Manner in Mouse Models of Amyloidosis.CNS neuroscience & therapeutics · 2026Article
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Metformin Ameliorates Cognitive Deficits and Neuroinflammation in a Mouse Model of Familial Hypercholesterolemia.Neurochemical research · 2026Article
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease and future strategies for targeted therapy.European journal of medical research · 2025Review
- 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
- The Role of Glial Cell Senescence in Alzheimer's Disease.Journal of neurochemistry · 2025Review
- Depth-dependent contributions of various vascular zones to cerebral autoregulation and functional hyperemia: An in-silico analysis.PloS one · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Near-lifespan mesoscopic optical imaging of cerebrovascular function reveals age and sex differences in preclinical Alzheimer's disease model.Brain communications · 2025Article
- The intricate interplay between dietary habits and cognitive function: insights from the gut-brain axis.Frontiers in nutrition · 2025Review
- Mechanistic Insights and Emerging Therapeutic Targets of Alzheimer's Disease: From the Perspective of Inter-Organ Crosstalk.Aging and disease · 2024Review
- Review
- Role of AMPK and Sirtuins in Aging Heart: Basic and Translational Aspects.Aging and disease · 2024Review
- USP9X-mediated deubiquitination of Raptor contributes to autophagy impairment and memory deficits in P301S mice.Cell communication and signaling : CCS · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
Vascular dysfunction is a universal feature of aging and decreased cerebral blood flow has been identified as an early event in the pathogenesis of Alzheimer's disease (AD). Cerebrovascular dysfunction in AD includes deficits in neurovascular coupling (NVC), a mechanism that ensures rapid delivery of energy substrates to active neurons through the blood supply. The mechanisms underlying NVC impairment in AD, however, are not well understood. We have previously shown that mechanistic/mammalian target of rapamycin (mTOR) drives cerebrovascular dysfunction in models of AD by reducing the activity of endothelial nitric oxide synthase (eNOS), and that attenuation of mTOR activity with rapamycin is sufficient to restore eNOS-dependent cerebrovascular function. Here we show mTOR drives NVC impairments in an AD model through the inhibition of neuronal NOS (nNOS)- and non-NOS-dependent components of NVC, and that mTOR attenuation with rapamycin is sufficient to restore NVC and even enhance it above WT responses. Restoration of NVC and concomitant reduction of cortical amyloid-β levels effectively treated memory deficits in 12-month-old hAPP(J20) mice. These data indicate that mTOR is a critical driver of NVC dysfunction and underlies cognitive impairment in an AD model. Together with our previous findings, the present studies suggest that mTOR promotes cerebrovascular dysfunction in AD, which is associated with early disruption of nNOS activation, through its broad negative impact on nNOS as well as on non-NOS components of NVC. Our studies highlight the potential of mTOR attenuation as an efficacious treatment for AD and potentially other neurologic diseases of aging.
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