ArticleScience (New York, N.Y.)2024
Restoring hippocampal glucose metabolism rescues cognition across Alzheimer's disease pathologies.
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Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
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138citing papers in PubMed, 1 pooled it
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Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between FDG- and TSPO-PET signals across human and animal studies investigating neurodegenerative conditions: a systematic review.Molecular psychiatry · 2026Pooled it
- Neuroimaging of indoleamine 2,3-dioxygenase 1 (Ido1) in Alzheimer's disease: Development of a novelMaterials today. Bio · 2026Article
- RIPK1 Links Metabolic Stresses to Inflammatory and Degenerative Pathways in Alzheimer's Disease.Neuroscience bulletin · 2026Article
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Trans-activator of transcription-pre-B-cell leukemia transcription factor 1 alleviates Alzheimer's disease by reducing neuronal insulin resistance and restoring energy homeostasis.Neural regeneration research · 2026Article
- Tryptophan Metabolism in Digestive and Extra-Digestive Diseases: Mechanisms, Clinical Implications, and Therapeutic Perspectives.Nutrients · 2026Review
- Mannan-oligosaccharides-based self-assembly nanoparticles enable gut-specific quercetin release, providing multi-pathway protection against AD via gut-brain axis.Journal of pharmaceutical analysis · 2026Article
- Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains.Cell reports. Medicine · 2026Article
- The sleep-wake cycle: molecular mechanisms, disorders, and therapeutic targets in the context of energy metabolism.Signal transduction and targeted therapy · 2026Review
- Electroacupuncture Improves the Learning and Memory by Modulating Hippocampal Glucose Metabolism through IGF1/IGF1R Signaling in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Docking Analysis of Drugs Used in the Treatment of Alzheimer's Disease, Using Cell Membrane Receptors and Enzymes of the Kynurenine Pathway: A Pilot Study.International journal of molecular sciences · 2026Article
- The liver-brain axis: A multidimensional regulatory network implicated in Alzheimer's disease pathogenesis and clinical implications.Animal models and experimental medicine · 2026Review
- The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models.International journal of molecular sciences · 2026Review
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- PYGL-driven glycogenolysis impairs microglial autophagic fluxActa pharmaceutica Sinica. B · 2026Article
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Hyperglycosylation is a metabolic driver of Alzheimer's disease.Nature metabolism · 2026Article
- Variants in glycine decarboxylase activate catabolic mechanisms of mitochondrial energy metabolism in the brain.The Journal of biological chemistry · 2026Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors.
Paras S Minhas *Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-7741-3327
Jeffrey R Jones *Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0000-0002-7570-2571
Amira Latif-Hernandez *Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Yuki SugiuraCentral Institute for Experimental Medicine and Life Science, Keio University, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.ORCID 0000-0002-6983-8958
Aarooran S DurairajDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0001-9355-3111
Qian WangDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0009-0003-6246-883X
Siddhita D MhatreDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0001-9939-780X
Takeshi UenakaDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0001-5786-5038
Joshua CrapserDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-8426-2336
Travis ConleyDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-9385-1386
Hannah EnnerfeltDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0003-4861-0740
Yoo Jin JungDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-9015-5529
Ling LiuLewis Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.
Praveena PrasadDepartment of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.ORCID 0009-0002-1485-4798
Brenita C JenkinsDepartment of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.ORCID 0000-0002-0354-8843
Yeonglong Albert AyDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0009-0000-2255-3042
Matthew MatrongoloDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Ryan GoodmanLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0009-0007-4828-2675
Traci NewmeyerLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Kelly HeardLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0000-0001-7719-7225
Austin KangLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0009-0007-0288-3029
Edward N WilsonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0003-0640-5247
Tao YangDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-7698-3440
Erik M UllianDepartment of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0003-2077-8584
Geidy E SerranoCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ 85351, USA.ORCID 0000-0002-9527-2011
Thomas G BeachCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ 85351, USA.ORCID 0000-0003-3296-6128
Marius WernigDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-5309-515X
Joshua D RabinowitzLewis Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.ORCID 0000-0002-1247-4727
Makoto SuematsuCentral Institute for Experimental Medicine and Life Science, Keio University, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.ORCID 0000-0002-7165-6336
Frank M LongoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-9514-7325
Melanie R McReynoldsLewis Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.ORCID 0000-0001-5427-2739
Fred H GageLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0000-0002-0938-4106
Katrin I AndreassonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0001-8391-4155
Funding
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8MResearch Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5MStanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0MNational Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8MNeuronal senescence and inflammation in Alzheimer's diseaseR37AG072502 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI FRED H GAGE · 2021 to 2026
$2.8MConProject-002RF1AG056306 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GAGE, FRED H · 2022 to 2025
$2.8MTargeting the kynurenine pathway in Alzheimer's diseaseR01AG048232 · NIA · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I. · 2014 to 2018
$2.4MRegulation of immune cell metabolism in aging and Alzheimer's disease: role of the kynurenine pathwayRF1AG058047 · NIA · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I. · 2017 to 2017
$2.0MNIA NIH HHS P30 AG019610NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066515NIA NIH HHS R01 AG048232NIA NIH HHS R37 AG072502NIA NIH HHS RF1 AG056306NIA NIH HHS RF1 AG058047NIGMS NIH HHS T32 GM007365NINDS NIH HHS U24 NS072026
Abstract
Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer's disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of astrocytic IDO1 by amyloid β and tau oligomers increases KYN and suppresses glycolysis in an aryl hydrocarbon receptor-dependent manner. In amyloid and tau models, IDO1 inhibition improves hippocampal glucose metabolism and rescues hippocampal long-term potentiation in a monocarboxylate transporter-dependent manner. In astrocytic and neuronal cocultures from AD subjects, IDO1 inhibition improved astrocytic production of lactate and uptake by neurons. Thus, IDO1 inhibitors presently developed for cancer might be repurposed for treatment of AD.
Indexed as
Alzheimer DiseaseAmyloid beta-PeptidesAstrocytesGlucoseGlycolysisHippocampusIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineNeuronsAnimalsCognitionDisease Models, AnimalHumansLactic AcidLong-Term PotentiationMaleAmyloid beta-PeptidesGlucoseIDO1 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineLactic AcidMonocarboxylic Acid TransportersReceptors, Aryl Hydrocarbontau ProteinsTryptophan
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