Abstract
Current mouse models of Alzheimers disease show brain pathology that correlates to a degree with memory impairment, but underlying molecular mechanisms remained unknown. Here we report studies with three lines of transgenic mice: animals that doubly express mutated human amyloid precursor protein (APPswe) and human acetylcholinesterase (hAChE); and animals transgenic for only the APPswe or the hAChE. Among these genotypes, variations were observed in expression of mRNA for presenilin-1, which was highest in singly transgenic hAChE mice, and the stressinducible form of AChE, which was elevated when both transgenes were present. At the age of nine months, both double and single transgenic mice displayed working memory impairment in a radial arm water maze. However, as compared with mice expressing amyloid alone, the double transgenic animals exhibited more numerous plaques and greater amyloid burden in brain (both by histochemistry and by ELISA of amyloid protein). Moreover, the amyloid burden in double transgenics was tightly correlated with memory impairment as measured by total maze errors (r2 = 0.78, p = .002). This correlation was markedly stronger than observed in mice with amyloid alone. These new findings support the notion of cholinergic-amyloid interrelationships and highlight the double transgenic mice as a promising alternative for testing Alzheimers therapies.
Keywords: alzheimers disease, acetylcholinesterase variants, amyloid precursor protein, cerebral cortex, hippocampus, presenilin
Current Alzheimer Research
Title: Memory Deficits Correlating with Acetylcholinesterase Splice Shift and Amyloid Burden in Doubly Transgenic Mice
Volume: 2 Issue: 3
Author(s): Tina M. Rees, Amit Berson, Ella H. Sklan, Linda Younkin, Steven Younkin, Stephen Brimijoin and Hermona Soreq
Affiliation:
Keywords: alzheimers disease, acetylcholinesterase variants, amyloid precursor protein, cerebral cortex, hippocampus, presenilin
Abstract: Current mouse models of Alzheimers disease show brain pathology that correlates to a degree with memory impairment, but underlying molecular mechanisms remained unknown. Here we report studies with three lines of transgenic mice: animals that doubly express mutated human amyloid precursor protein (APPswe) and human acetylcholinesterase (hAChE); and animals transgenic for only the APPswe or the hAChE. Among these genotypes, variations were observed in expression of mRNA for presenilin-1, which was highest in singly transgenic hAChE mice, and the stressinducible form of AChE, which was elevated when both transgenes were present. At the age of nine months, both double and single transgenic mice displayed working memory impairment in a radial arm water maze. However, as compared with mice expressing amyloid alone, the double transgenic animals exhibited more numerous plaques and greater amyloid burden in brain (both by histochemistry and by ELISA of amyloid protein). Moreover, the amyloid burden in double transgenics was tightly correlated with memory impairment as measured by total maze errors (r2 = 0.78, p = .002). This correlation was markedly stronger than observed in mice with amyloid alone. These new findings support the notion of cholinergic-amyloid interrelationships and highlight the double transgenic mice as a promising alternative for testing Alzheimers therapies.
Export Options
About this article
Cite this article as:
Rees M. Tina, Berson Amit, Sklan H. Ella, Younkin Linda, Younkin Steven, Brimijoin Stephen and Soreq Hermona, Memory Deficits Correlating with Acetylcholinesterase Splice Shift and Amyloid Burden in Doubly Transgenic Mice, Current Alzheimer Research 2005; 2 (3) . https://dx.doi.org/10.2174/1567205054367847
DOI https://dx.doi.org/10.2174/1567205054367847 |
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
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...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
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Chemo-botanical and Neurological Accounts of Some Ayurvedic Plants Useful in Mental Health
The Natural Products Journal Chemistry and Pharmacology of Bioactive Molecule -Coenzyme Q10: A Brief Note
Current Bioactive Compounds Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview
Current Medicinal Chemistry Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies
Current Pharmaceutical Design Biotechnological Engineering of Heparin/Heparan Sulphate: A Novel Area of Multi-Target Drug Discovery
Current Pharmaceutical Design Modulatory Effects of pH, Cu+2 and Sheet Breakers on Aggregation of Amyloid Peptides
Protein & Peptide Letters Oxidative Stress and Pathophysiology of Ischemic Stroke: Novel Therapeutic Opportunities
CNS & Neurological Disorders - Drug Targets Kinetic Study on the Effects of Extremely Low Frequency Electromagnetic Field on Catalase, Cytochrome P450 and Inducible Nitric Oxide Synthase in Human HaCaT and THP-1 Cell Lines
CNS & Neurological Disorders - Drug Targets Molecular Imaging in the Default Mode Network
Current Molecular Imaging (Discontinued) Synthesis of Novel 4-(Dimethylaminoalkyl)piperazine-1-carbodithioa t e Derivatives as Cholinesterase Inhibitors
Letters in Drug Design & Discovery Understanding the Multifaceted Role of Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) and its Altered Behaviour in Human Diseases
Current Molecular Medicine Complementary and Alternative Medicine for the Treatment of Insomnia: An Overview of Scientific Evidence from 2008 to 2018
Current Vascular Pharmacology Children with Chronic Kidney Disease and Hypertension: Could Hypertension Footprints be Early Biomarkers?
Current Hypertension Reviews Astroglial Connexins in Neurological and Neuropsychological Disorders and Radiation Exposure
Current Medicinal Chemistry The Role of the Catechol-o-Methyltransferase (COMT) GeneVal158Met in Aggressive Behavior, a Review of Genetic Studies
Current Neuropharmacology Nicotinic Acetylcholine Receptors as Drug Targets
Current Drug Targets - CNS & Neurological Disorders Zolpidem Therapy for Movement Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Anti-TNF Treatment in Rheumatoid Arthritis
Current Pharmaceutical Design The Complement Cascade: New Avenues in Stroke Therapy
Current Vascular Pharmacology Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders
Current Alzheimer Research