ArticleJournal of Alzheimer's disease : JAD2019
Global Metabolic Shifts in Age and Alzheimer's Disease Mouse Brains Pivot at NAD+/NADH Redox Sites.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 85 citations in OpenAlex.
- Breaking the age-related redox spiral for regeneration.Neural regeneration research · 2026Article
- Metabolomics Analysis Revealed That SXZ Ameliorates Cognitive Impairment in Naturally Aged Rats by Promoting Glutathione Metabolism and Inhibiting the Ferroptosis Pathway.CNS neuroscience & therapeutics · 2026Article
- The Reductive Stress Nexus: Integrated Pathways of Metabolic Dysregulation, Senescence and Blood-Brain Barrier Failure in Neurodegenerative Disease and Brain Aging.Cell biochemistry and biophysics · 2026Review
- A combined artificial intelligence-wet lab approach identifies a pivotal role of the NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Redox Molecules in Aging and Neurodegenerative Disorders.International journal of molecular sciences · 2026Review
- Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain.Cell reports. Medicine · 2026Article
- Changes in the brain [NADFrontiers in aging neuroscience · 2026Review
- NADScience advances · 2025Article
- Transcranial near infrared therapy reprograms metabolism to rescue sleep and place cell functionality.iScience · 2025Article
- A multiscale electro-metabolic model of a rat neocortical circuit reveals the impact of ageing on central cortical layers.PLoS computational biology · 2025Article
- Inhibition of the cGAS-STING pathwayChemical science · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Programmed neurite degeneration in human central nervous system neurons driven by changes in NADCell death & disease · 2025Article
- Quantitative analysis of serum metabolites in a rat model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- Unique tau- and synuclein-dependent metabolic reprogramming in neurons distinct from normal aging.Aging cell · 2024Article
- Intestinal endogenous metabolites affect neuroinflammation in 5×FAD mice by mediating "gut-brain" axis and the intervention with Chinese Medicine.Alzheimer's research & therapy · 2024Article
- Identification of blood metabolites associated with risk of Alzheimer's disease by integrating genomics and metabolomics data.Molecular psychiatry · 2024Article
- Roles of NADCold Spring Harbor perspectives in medicine · 2024Review
- Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases.International journal of molecular sciences · 2023Review
- Shared metabolic shifts in endothelial cells in stroke and Alzheimer's disease revealed by integrated analysis.Scientific data · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Age and Alzheimer's disease (AD) share some common features such as cognitive impairments, memory loss, metabolic disturbances, bioenergetic deficits, and inflammation. Yet little is known on how systematic shifts in metabolic networks depend on age and AD. In this work, we investigated the global metabolomic alterations in non-transgenic (NTg) and triple-transgenic (3xTg-AD) mouse brain hippocampus as a function of age by using untargeted Ultrahigh Performance Liquid Chromatography-tandem Mass Spectroscopy (UPLC-MS/MS). We observed common metabolic patterns with aging in both NTg and 3xTg-AD brains involved in energy-generating pathways, fatty acids oxidation, glutamate, and sphingolipid metabolism. We found age-related downregulation of metabolites from reactions in glycolysis that consumed ATP and in the TCA cycle, especially at NAD+/NADH-dependent redox sites, where age- and AD-associated limitations in the free NADH may alter reactions. Conversely, metabolites increased in glycolytic reactions in which ATP is produced. With age, inputs to the TCA cycle were increased including fatty acid β-oxidation and glutamine. Overall age- and AD-related changes were > 2-fold when comparing the declines of upstream metabolites of NAD+/NADH-dependent reactions to the increases of downstream metabolites (p = 10-5, n = 8 redox reactions). Inflammatory metabolites such as ceramides and sphingosine-1-phosphate also increased with age. Age-related decreases in glutamate, GABA, and sphingolipid were seen which worsened with AD genetic load in 3xTg-AD brains, possibly contributing to synaptic, learning- and memory-related deficits. The data support the novel hypothesis that age- and AD-associated metabolic shifts respond to NAD(P)+/NAD(P)H redox-dependent reactions, which may contribute to decreased energetic capacity.
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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.