Abstract
Apolipoprotein E (APOE) genetic variation and aging are the two most noted risk factors associated with the development of Alzheimer’s disease (AD) related dementia. However, the relationship between these two pathological factors is not understood. Formaldehyde (FA) is an age related factor that has been found to be elevated in AD patients and is known to have protein cross-linking properties. FA forms cross-links with larger arginine, lysine and tryptophan residues but also has thiol reactivity. This study investigated the formation of protein aggregates between amyloid-beta (1-40) peptide (Aβ), the main component of amyloid plaques in AD, with APOE isoforms in vitro. APOE4 protein, the isoform with arginines at residue 112 and 158, was found to form aggregates with more Aβ (P < 0.001) and APOE (P < 0.05) protein content in 10 mM FA than aggregates formed with either APOE3 or APOE2 protein. This aggregation pattern reflected the trend of vulnerability conferred by the APOE genetic variation (APOE4 > APOE3 > APOE2) and suggested that FA may have a role in the differential pattern of amyloid plaque formation in people with differing APOE genetic backgrounds. All told, this finding adds to a growing body of evidence that FA has a role in AD progression as well as provides a novel link between aging and APOE risk factors; the cornerstones of one of the world’s largest mental health concerns.
Keywords: Aggregation, Alzheimer's disease, amyloid-beta, apolipoprotein E isoforms, formaldehyde, plaque formation.
Current Alzheimer Research
Title:Is Formaldehyde the Missing Link in AD Pathology? The Differential Aggregation of Amyloid-Beta with APOE Isoforms In Vitro
Volume: 11 Issue: 5
Author(s): Joshua D. Rizak, Yuanye Ma and Xintian Hu
Affiliation:
Keywords: Aggregation, Alzheimer's disease, amyloid-beta, apolipoprotein E isoforms, formaldehyde, plaque formation.
Abstract: Apolipoprotein E (APOE) genetic variation and aging are the two most noted risk factors associated with the development of Alzheimer’s disease (AD) related dementia. However, the relationship between these two pathological factors is not understood. Formaldehyde (FA) is an age related factor that has been found to be elevated in AD patients and is known to have protein cross-linking properties. FA forms cross-links with larger arginine, lysine and tryptophan residues but also has thiol reactivity. This study investigated the formation of protein aggregates between amyloid-beta (1-40) peptide (Aβ), the main component of amyloid plaques in AD, with APOE isoforms in vitro. APOE4 protein, the isoform with arginines at residue 112 and 158, was found to form aggregates with more Aβ (P < 0.001) and APOE (P < 0.05) protein content in 10 mM FA than aggregates formed with either APOE3 or APOE2 protein. This aggregation pattern reflected the trend of vulnerability conferred by the APOE genetic variation (APOE4 > APOE3 > APOE2) and suggested that FA may have a role in the differential pattern of amyloid plaque formation in people with differing APOE genetic backgrounds. All told, this finding adds to a growing body of evidence that FA has a role in AD progression as well as provides a novel link between aging and APOE risk factors; the cornerstones of one of the world’s largest mental health concerns.
Export Options
About this article
Cite this article as:
Rizak D. Joshua, Ma Yuanye and Hu Xintian, Is Formaldehyde the Missing Link in AD Pathology? The Differential Aggregation of Amyloid-Beta with APOE Isoforms In Vitro, Current Alzheimer Research 2014; 11 (5) . https://dx.doi.org/10.2174/1567205011666140425112043
DOI https://dx.doi.org/10.2174/1567205011666140425112043 |
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
- 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
- Homocysteine Enhances Transmigration of Rat Monocytes through a Brain Capillary Endothelial Cell Monolayer via ICAM-1
Current Neurovascular Research Understanding Membrane Protein Drug Targets in Computational Perspective
Current Drug Targets The Promises and Challenges of the Use of Genomics in the Prescription of Exercise for Hypertension: The 2013 Update
Current Hypertension Reviews Editorial: [Aliskiren/Amlodipine Single-Pill Combinations: More Evidence in Favour of Combination Formulations for the Treatment of Hypertension]
Current Vascular Pharmacology Therapeutic Applications of Human Heme Oxygenase Gene Transfer and Gene Therapy
Current Pharmaceutical Design Specific Nutritional Needs for Children. Are Children Small Adults?
Current Nutrition & Food Science Antiangiogenic Agents: Studies on Fumagillin and Curcumin Analogs
Current Pharmaceutical Design Mediators of Low-Grade Chronic Inflammation in Polycystic Ovary Syndrome (PCOS)
Current Pharmaceutical Design Meet the Editorial Board Member
Current Drug Targets Autologous Circulating Progenitor Cells Transplanted with Hybrid Scaffold Accelerate Diabetic Wound Healing in Rabbit Model
Current Tissue Engineering (Discontinued) Drug Development and the Importance of Ethnicity: Lessons from Heart Failure Management and Implications for Hypertension
Current Pharmaceutical Design Omega-3 Polyunsaturated Fatty Acids in Alzheimers Disease: Key Questions and Partial Answers
Current Alzheimer Research Treatments for Obesity-Related Hypertension
Current Hypertension Reviews Cannabinoid Modulation of Perivascular Sympathetic and Sensory Neurotransmission
Current Vascular Pharmacology Identification of Neuronal Nitric Oxide Synthase (nNOS) in Human Penis: a Potential Role of Reduced Neuronally-derived Nitric Oxide in Erectile Dysfunction
Current Pharmaceutical Biotechnology Acute Coronary Syndromes as Auto-Inflammatory Disorders
Current Pharmaceutical Design Oxytocin and Diabetes Mellitus: A Strong Biochemical Relation. Review
Current Diabetes Reviews Effect on Serum Uric Acid Levels of Drugs Prescribed for Indications other than Treating Hyperuricaemia
Current Pharmaceutical Design Neurovascular Complications of Ovarian Hyperstimulation Syndrome (OHSS): From Pathophysiology to Recent Treatment Options
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Hypoglycemic Hemiparesis Masquerading As Ischemic Stroke: When Guideline Fails
Current Drug Therapy