Abstract
The role of microglia in β-amyloid (Aβ) deposition or clearance in the Alzheimer's disease (AD) brain remains unclear. Previous in vivo studies have focused primarily on the association of microglia with Aβ-positive parenchymal plaques, but have given little consideration to the possible interaction between Aβ and non-plaque associated microglia. Further, it is not known if microglia play a direct role in mediating Aβ uptake following anti-aggregant treatment. We report here the identification of Aβ-positive processes throughout the cortex and hippocampus of TgCRND8 mice expressing the human Swedish (KM670/671NL) and Indiana (V717F) amyloid precursor protein mutations, which localized to ionized calcium binding protein-1-positive resident microglia that were not associated with extracellular plaques. Oral administration of 1-deoxy-1-fluoro-scyllo-inositol, a scyllo-inositol analogue, to TgCRND8 mice improved spatial memory impairments and suppressed amyloid pathology in a dose-dependent manner. Further, treatment with 1-deoxy-1- fluoro-scyllo-inositol significantly increased hippocampal intra-microglial Aβ levels without stimulating microglial proliferation or peripheral macrophage recruitment. These results reveal a novel, beneficial role for non-plaque associated microglia in the regulation of cerebral Aβ levels in a mouse model of AD.
Keywords: Alzheimer’s disease, anti-aggregant, transgenic mouse model, Microglia, Immunoblotting, Central nervous system, β-amyloid, Glial fibrillary acidic protein
Current Alzheimer Research
Title:In Vivo Uptake of β-Amyloid by Non-Plaque Associated Microglia
Volume: 9 Issue: 8
Author(s): Cheryl A Hawkes, LeHua Deng, Daniela Fenili, Mark Nitz and JoAnne McLaurin
Affiliation:
Keywords: Alzheimer’s disease, anti-aggregant, transgenic mouse model, Microglia, Immunoblotting, Central nervous system, β-amyloid, Glial fibrillary acidic protein
Abstract: The role of microglia in β-amyloid (Aβ) deposition or clearance in the Alzheimer's disease (AD) brain remains unclear. Previous in vivo studies have focused primarily on the association of microglia with Aβ-positive parenchymal plaques, but have given little consideration to the possible interaction between Aβ and non-plaque associated microglia. Further, it is not known if microglia play a direct role in mediating Aβ uptake following anti-aggregant treatment. We report here the identification of Aβ-positive processes throughout the cortex and hippocampus of TgCRND8 mice expressing the human Swedish (KM670/671NL) and Indiana (V717F) amyloid precursor protein mutations, which localized to ionized calcium binding protein-1-positive resident microglia that were not associated with extracellular plaques. Oral administration of 1-deoxy-1-fluoro-scyllo-inositol, a scyllo-inositol analogue, to TgCRND8 mice improved spatial memory impairments and suppressed amyloid pathology in a dose-dependent manner. Further, treatment with 1-deoxy-1- fluoro-scyllo-inositol significantly increased hippocampal intra-microglial Aβ levels without stimulating microglial proliferation or peripheral macrophage recruitment. These results reveal a novel, beneficial role for non-plaque associated microglia in the regulation of cerebral Aβ levels in a mouse model of AD.
Export Options
About this article
Cite this article as:
A Hawkes Cheryl, Deng LeHua, Fenili Daniela, Nitz Mark and McLaurin JoAnne, In Vivo Uptake of β-Amyloid by Non-Plaque Associated Microglia, Current Alzheimer Research 2012; 9 (8) . https://dx.doi.org/10.2174/156720512803251084
DOI https://dx.doi.org/10.2174/156720512803251084 |
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
-
Non-Pharmacological Treatments for ADHD in Youth
Adolescent Psychiatry Therapeutic Challenges in Neuroendocrine Tumors
Anti-Cancer Agents in Medicinal Chemistry Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair
Current Pharmaceutical Design Hypoxia Inducible Factor 1 as a Therapeutic Target in Ischemic Stroke
Current Medicinal Chemistry The Role of Pro-Inflammatory Molecules and Pharmacological Agents in Acute Pancreatitis and Sepsis
Inflammation & Allergy - Drug Targets (Discontinued) Extrahepatic Targets and Cellular Reactivity of Drug Metabolites
Current Medicinal Chemistry Anti-cancer Therapies in High Grade Gliomas
Current Proteomics The Role of Oxidative Stress in Huntington’s Disease: Are Antioxidants Good Therapeutic Candidates?
Current Drug Targets Microbubbles as Drug Delivery Systems in Cerebrovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Phosphodiesterase as a New Therapeutic Target for the Treatment of Spinal Cord Injury and Neurodegenerative Diseases
Current Medicinal Chemistry Glycans and Glycan-Binding Proteins in Brain: Galectin-1-Induced Expression of Neurotrophic Factors in Astrocytes
Current Drug Targets Cannabinoids and Neuropathic Pain
Mini-Reviews in Medicinal Chemistry The Renin-Angiotensin System and the Cerebrovascular Diseases: Experimental and Clinical Evidence
Protein & Peptide Letters Genistein: A Boon for Mitigating Ischemic Stroke
Current Topics in Medicinal Chemistry Endothelin Receptor Antagonists: A New Therapeutic Option for Improving the Outcome after Solid Organ Transplantation?
Current Vascular Pharmacology Endogenous Regulation of Neural Stem Cells in the Adult Mammalian Brain
Central Nervous System Agents in Medicinal Chemistry Piribedil: Antiparkinsonian Properties and Potential Clinical Utility in Dopaminergic Disorders
Current Drug Therapy The Therapeutic Potential of Purinergic Receptors in Alzheimer’s Disease and Promising Therapeutic Modulators
Mini-Reviews in Medicinal Chemistry Non-Infectious Complications of Immunosuppressant Medications in Renal Transplant Patients
Current Clinical Pharmacology Editorial [Hot Topic: Innate Immune Responses in CNS Neurodegenerative Diseases (Guest Editors: Hans van Noort and Sandra Amor)]
CNS & Neurological Disorders - Drug Targets