Abstract
Positron emission tomography studies of cerebral glucose utilization and amyloid-β deposition with fluoro-deoxy-D-glucose ([18F]-FDG) and amyloid tracers have shown characteristic pathological changes in Alzheimer’s Disease that can be used for disease diagnosis and monitoring. Application of this technology to preclinical research with transgenic animal models would greatly facilitate drug discovery and further understanding of disease processes. The results from preclinical studies with these imaging biomarkers have however been highly inconsistent, causing doubts over whether animal models can truly replicate an AD-like phenotype. In this study we performed in vivo imaging with [18F]-FDG and [18F]-AV45 in double transgenic TASTPM mice, a transgenic model that been previously demonstrated high levels of fibrillar amyloid-β and decreases in cerebral glucose utilization with ex vivo techniques. Our results show widespread and significant retention of [18F]-AV45 (p < 0.0001) in aged TASTPM mice in addition to significantregional decreases in [18F]-FDG uptake (p < 0.05). In vivo quantification of amyloid-β showed a strong (Pearson’s r = 0.7078), but not significant (p = 0.1156), positive correlation with ex vivo measures suggesting some limitations on tracer sensitivity. In the case of [18F]-FDG, voxelwise analysis greatly enhanced detection of hypometabolic regions. We further evidenced modest neuronal loss (thalamus p = 0.0318) that could underlie the observed hypometabolism. This research was performed in conjunction with the European Community's Seventh Framework Program (FP7/2007-2013) for the Innovative Medicine Initiative under the PharmaCog Grant Agreement no.115009.
Keywords: [18F]-AV45, [18F]-FDG, animal models, Alzheimer’s Disease, biomarker, positron emission tomography.
Current Alzheimer Research
Title:Quantitative μPET Imaging of Cerebral Glucose Metabolism and Amyloidosis in the TASTPM Double Transgenic Mouse Model of Alzheimer’s Disease
Volume: 12 Issue: 7
Author(s): Ann-Marie Waldron, Leonie Wyffels, Jeroen Verhaeghe, Astrid Bottelbergs, Jill Richardson, Jonathan Kelley, Mark Schmidt, Sigrid Stroobants, Xavier Langlois and Steven Staelens
Affiliation:
Keywords: [18F]-AV45, [18F]-FDG, animal models, Alzheimer’s Disease, biomarker, positron emission tomography.
Abstract: Positron emission tomography studies of cerebral glucose utilization and amyloid-β deposition with fluoro-deoxy-D-glucose ([18F]-FDG) and amyloid tracers have shown characteristic pathological changes in Alzheimer’s Disease that can be used for disease diagnosis and monitoring. Application of this technology to preclinical research with transgenic animal models would greatly facilitate drug discovery and further understanding of disease processes. The results from preclinical studies with these imaging biomarkers have however been highly inconsistent, causing doubts over whether animal models can truly replicate an AD-like phenotype. In this study we performed in vivo imaging with [18F]-FDG and [18F]-AV45 in double transgenic TASTPM mice, a transgenic model that been previously demonstrated high levels of fibrillar amyloid-β and decreases in cerebral glucose utilization with ex vivo techniques. Our results show widespread and significant retention of [18F]-AV45 (p < 0.0001) in aged TASTPM mice in addition to significantregional decreases in [18F]-FDG uptake (p < 0.05). In vivo quantification of amyloid-β showed a strong (Pearson’s r = 0.7078), but not significant (p = 0.1156), positive correlation with ex vivo measures suggesting some limitations on tracer sensitivity. In the case of [18F]-FDG, voxelwise analysis greatly enhanced detection of hypometabolic regions. We further evidenced modest neuronal loss (thalamus p = 0.0318) that could underlie the observed hypometabolism. This research was performed in conjunction with the European Community's Seventh Framework Program (FP7/2007-2013) for the Innovative Medicine Initiative under the PharmaCog Grant Agreement no.115009.
Export Options
About this article
Cite this article as:
Waldron Ann-Marie, Wyffels Leonie, Verhaeghe Jeroen, Bottelbergs Astrid, Richardson Jill, Kelley Jonathan, Schmidt Mark, Stroobants Sigrid, Langlois Xavier and Staelens Steven, Quantitative μPET Imaging of Cerebral Glucose Metabolism and Amyloidosis in the TASTPM Double Transgenic Mouse Model of Alzheimer’s Disease, Current Alzheimer Research 2015; 12 (7) . https://dx.doi.org/10.2174/1567205012666150710104713
DOI https://dx.doi.org/10.2174/1567205012666150710104713 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Medicinal and Beneficial Health Applications of Tinospora cordifolia (Guduchi): A Miraculous Herb Countering Various Diseases/Disorders and its Immunomodulatory Effects
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Lithium - Pharmacological and Toxicological Aspects: The Current State of the Art
Current Medicinal Chemistry Effect of Simvastatin on Inflammatory Cytokines Balance in Air Pouch Granuloma Model
Inflammation & Allergy - Drug Targets (Discontinued) Meet the Editorial Board Members
Current HIV Research Transcranial Direct Current Stimulation for Treatment of Alzheimer’s Disease: A Systematic Review of Randomized Clinical Trial
Current Psychiatry Reviews Treatment of Chronic Myeloid Leukemia Elderly Patients in the Tyrosine Kinase Inhibitor Era
Current Cancer Drug Targets A1 Receptors Ligands: Past, Present and Future Trends
Current Topics in Medicinal Chemistry Role of Ischemic Blood-Brain Barrier on Amyloid Plaques Development in Alzheimers Disease Brain
Current Neurovascular Research A Synthesis of Functional Neuroimaging in the Frontal Variant of Frontotemporal Dementia
Current Medical Imaging Potential Drugs Targeting Microglia: Current Knowledge and Future Prospects
CNS & Neurological Disorders - Drug Targets Tau Oligomerization: A Role for Tau Aggregation Intermediates Linked to Neurodegeneration
Current Alzheimer Research Fish Oil has Beneficial Effects on Behavior Impairment and Oxidative Stress in Rats Subjected to a Hepatic Encephalopathy Model
CNS & Neurological Disorders - Drug Targets Inflammatory Process as a Determinant Factor for the Degeneration of Substantia Nigra Dopaminergic Neurons: Possible Relevance to the Etiology of Parkinsons Disease
Current Medicinal Chemistry - Central Nervous System Agents D1 and Functionally Selective Dopamine Agonists as Neuroprotective Agents in Parkinsons Disease
CNS & Neurological Disorders - Drug Targets Vasoactive Intestinal Peptide in Neurodevelopmental Disorders:Therapeutic Potential
Current Pharmaceutical Design Estrogenic Compounds, Estrogen Receptors and Vascular Cell Signaling in the Aging Blood Vessels
Current Medicinal Chemistry Hormone Replacement Therapy in Rheumatoid Arthritis
Current Rheumatology Reviews Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy Alzheimer’s Disorder: Epigenetic Connection and Associated Risk Factors
Current Neuropharmacology Neuroprotective Actions of Flavones and Flavonols: Mechanisms and Relationship to Flavonoid Structural Features
Central Nervous System Agents in Medicinal Chemistry