ArticleJournal of neurochemistry2021
Sex-specific alterations in NAD+ metabolism in 3xTg Alzheimer's disease mouse brain assessed by quantitative targeted LC-MS.
Article in Journal of neurochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Western diet-induced MASH in PWK/PhJ mice identifies disruptions in amino acid and sphingolipid metabolism contributing to cardiac dysfunction.Nature communications · 2026Article
- Decoding the Metabolic Signatures of Neurodegeneration Diseases: Advances in Mass Spectrometry-Based Metabolomics.Metabolites · 2026Review
- Perturbation of NAD(P)H metabolism with theScience advances · 2026Article
- Chemotherapy-driven intestinal dysbiosis and indole-3-propionic acid rewire myelopoiesis to promote a metastasis-refractory state.Nature communications · 2025Article
- The Role of NADAmerican journal of cardiovascular drugs : drugs, devices, and other interventions · 2025Review
- Review
- ACMSD inhibition corrects fibrosis, inflammation, and DNA damage in MASLD/MASH.Journal of hepatology · 2025Article
- Tissue-specific modulation of NADH consumption as an anti-aging intervention in Drosophila.bioRxiv : the preprint server for biology · 2025Article
- Altered Heme and Redox Homeostasis Underpin Late-onset Alzheimer's Disease.International journal of biological sciences · 2025Article
- Effect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβJournal of neurochemistry · 2025Article
- Autophagy-NADFrontiers in molecular biosciences · 2025Review
- Alzheimer's disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway.Alzheimer's research & therapy · 2024Article
- NADCell death & disease · 2024Article
- Article
- Sex-specific associations of kynurenic acid with neopterin in Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Targeting NAD Metabolism for the Therapy of Age-Related Neurodegenerative Diseases.Neuroscience bulletin · 2024Review
- Microglial immunometabolism endophenotypes contribute to sex difference in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Hepatocyte nuclear factor 4α mediated quinolinate phosphoribosylltransferase (QPRT) expression in the kidney facilitates resilience against acute kidney injury.Kidney international · 2023Article
- The Combination of Citicoline and Nicotinamide Mononucleotide Induces Neurite Outgrowth and Mitigates Vascular Cognitive Impairment via SIRT1/CREB Pathway.Cellular and molecular neurobiology · 2023Article
- Axonal energy metabolism, and the effects in aging and neurodegenerative diseases.Molecular neurodegeneration · 2023Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Levels of nicotinamide adenine dinucleotide (NAD+) are known to decline with age and have been associated with impaired mitochondrial function leading to neurodegeneration, a key facet of Alzheimer's disease (AD). NAD+synthesis is sustained via tryptophan-kynurenine (Trp-Kyn) pathway as de novo synthesis route, and salvage pathways dependent on the availability of nicotinic acid and nicotinamide. While being currently investigated as a multifactorial disease with a strong metabolic component, AD remains without curative treatment and important sex differences were reported in relation to disease onset and progression. The aim of this study was to reveal the potential deregulation of NAD+metabolism in AD with the direct analysis of NAD+precursors in the mouse brain tissue (wild type (WT) versus triple transgenic (3xTg) AD), using a sex-balanced design. To this end, we developed a quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which allowed for the measurement of the full spectrum of NAD+precursors and intermediates in all three pathways. In brain tissue of mice with developed AD symptoms, a decrease in kynurenine (Kyn) versus increase in kynurenic acid (KA) levels were observed in both sexes with a significantly higher increment of KA in males. These alterations in Trp-Kyn pathway might be a consequence of neuroinflammation and a compensatory production of neuroprotective kynurenic acid. In the NAD+ salvage pathway, significantly lower levels of nicotinamide mononucleotide (NMN) were measured in the AD brain of males and females. Depletion of NMN implies the deregulation of salvage pathway critical for maintaining optimal NAD+ levels and mitochondrial and neuronal function.
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