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...
| Publicado en: | Frontiers in Aging Neuroscience pp. 1 - 15 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Frontiers Media S.A.
2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=193228435&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 193228435 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16634365 BG2U jtl: Frontiers in Aging Neuroscience issn: 16634365 maglogo: N pubinfo: dt: 2026 pid: 40038 pub: Frontiers Media S.A. artinfo: ui: 193228435 193228435 193228435 10.3389/fnagi.2026.1710075 193228435 ppf: 1 ppct: 14 formats: tig: atl: Dysregulated glucose metabolism in the visual cortex of human subjects with mild cognitive impairment and Alzheimer's disease. aug: 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 refInfo: holdings: @attributes: islocal: N |
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