Dysregulated glucose metabolism in the visual cortex of human subjects with mild cognitive impairment and Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired glucose metabolism. While most studies focus on heavily affected brain regions such as the hippocampus and prefrontal cortex, the visual cortex remains relatively preserved in early AD and provides...

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Publicado en:Frontiers in Aging Neuroscience pp. 1 - 15
Autores principales: Mjaaseth, Ulrik N., Hsu, Ming-Fo, Arballo, Joseph, Haj, Fawaz G., Patel, Viharkumar
Formato: research tables/charts Journal Article
Publicado: Frontiers Media S.A. 2026
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: Frontiers in Aging Neuroscience
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      dt: 2026
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      pub: Frontiers Media S.A.
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        193228435
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        10.3389/fnagi.2026.1710075
        193228435
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        atl: Dysregulated glucose metabolism in the visual cortex of human subjects with mild cognitive impairment and Alzheimer's disease.
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        au:
          Mjaaseth, Ulrik N.
          Hsu, Ming-Fo
          Arballo, Joseph
          Haj, Fawaz G.
          Patel, Viharkumar
        affil: Department of Nutrition, University of California, Davis, Davis, CA, United States
      sug:
        subj:
          Occipital Lobe Metabolism
          Mild Cognitive Impairment Metabolism
          Alzheimer's Disease Physiopathology
          Alzheimer's Disease Metabolism
          Glucose Metabolism
          Gene Expression
          Metabolomics
          Autopsy
          Human
          Male
          Female
          Middle Age
          Aged
          Aged, 80 and Over
          Funding Source
          Reverse Transcriptase Polymerase Chain Reaction
          T-Tests
          Kruskal-Wallis Test
          Post Hoc Analysis
          Spearman's Rank Correlation Coefficient
          Data Analysis Software
          Descriptive Statistics
          Liquid Chromatography-Mass Spectrometry
          Tumor Necrosis Factor
          Brain Metabolism
          Middle Aged: 45-64 years
          Aged: 65+ years
          Aged, 80 & over
          Male
          Female
      ab: Introduction: Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired glucose metabolism. While most studies focus on heavily affected brain regions such as the hippocampus and prefrontal cortex, the visual cortex remains relatively preserved in early AD and provides an opportunity to examine metabolic alterations that precede widespread pathology. Methods: Postmortem human visual cortex samples were obtained from control, mild cognitive impairment (MCI), and AD subjects without non-AD neuropathologic conditions. Untargeted metabolomics was performed using liquid chromatography–mass spectrometry, and expression of key metabolic, inflammatory, and AD-related genes was measured by quantitative PCR. Data analysis was conducted using MetaboAnalyst and R. Results: Metabolomic profiling revealed progressive disruptions in glucose metabolism, and mitochondrial function across MCI and AD subjects. Gene expression analyses showed reduced levels of glycolytic enzymes (HK1 , PFKM , PKM1), mitochondrial regulators (PDHA1 , NDUFC1), and the neuronal glucose transporter SLC2A3. Insulin signaling was altered, with decreased IDE and increased INSR and PTPN1 gene expression. Inflammatory markers including TNF , IL1B , and GFAP were elevated in AD. Sex-stratified analyses revealed both shared and distinct metabolic signatures, particularly within glucose and mitochondrial pathways. Several metabolic gene changes correlated negatively with Braak stage, highlighting a progressive decline in energy metabolism alongside tau pathology. Discussion: These findings demonstrate early and progressive metabolic dysfunction in the visual cortex of MCI and AD subjects. Even in a region with limited structural pathology, profound alterations in energy metabolism were observed, underscoring its central role in AD pathogenesis and highlighting improving neuronal metabolic function as a promising target for therapeutic intervention.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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