Abstract
Background: Formaldehyde (FA) has been implicated in Alzheimer’s disease (AD) pathology as an age-related factor and as a protein cross-linker known to aggregate Amyloid-Beta (Aβ) and tau protein in vitro. Higher levels of FA have also been found in patients with greater cognitive impairment and in AD patient brains.
Objective: To directly evaluate the effect of chronically elevated FA levels on the primate brain with respect to AD pathological markers.
Method: Young rhesus macaques (5-8 yrs, without AD related mutations) were given chronic intracerebroventricular (i.c.v.) injections of FA or vehicle over a 12-month period. Monkeys were monitored for changes in cognitive ability and evaluated post-mortem for common AD pathological markers.
Results: Monkeys injected with FA were found to have significant spatial working memory impairments. Histopathological analysis revealed the presence of amyloid-β+ neuritic-like plaques, neurofibrillary tangle-like formations, increased tau protein phosphorylation, neuronal loss and reactive gliosis in three memory (and AD) related brain areas (the hippocampus, entorhinal cortex and prefrontal cortex (PFC)) of monkeys receiving i.c.v. injections of FA. ELISA assays revealed that the amounts of pT181 and Aβ42 were markedly higher in the PFC and hippocampus of FA treated monkeys.
Conclusion: FA was found to induce major AD-like pathological markers and cognitive impairments in young rhesus monkeys independent of genetic predispositions. This suggests FA may play a significant role in the initiation and progression of the disease.
Keywords: Alzheimer's disease, formaldehyde, aggregation, neuritic plaques, neurofibrillary tangles, neuronal loss, reactive gliosis, monkeys.
Current Alzheimer Research
Title:Alzheimer's Disease-Like Pathologies and Cognitive Impairments Induced by Formaldehyde in Non-Human Primates
Volume: 15 Issue: 14
Author(s): Rongwei Zhai, Joshua Rizak, Na Zheng, Xiaping He, Zhenhui Li, Yong Yin, Tao Su, Yingge He, Rongqiao He, Yuanye Ma, Meifeng Yang*, Zhengbo Wang*Xintian Hu*
Affiliation:
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223,China
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223,China
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223,China
Keywords: Alzheimer's disease, formaldehyde, aggregation, neuritic plaques, neurofibrillary tangles, neuronal loss, reactive gliosis, monkeys.
Abstract: Background: Formaldehyde (FA) has been implicated in Alzheimer’s disease (AD) pathology as an age-related factor and as a protein cross-linker known to aggregate Amyloid-Beta (Aβ) and tau protein in vitro. Higher levels of FA have also been found in patients with greater cognitive impairment and in AD patient brains.
Objective: To directly evaluate the effect of chronically elevated FA levels on the primate brain with respect to AD pathological markers.
Method: Young rhesus macaques (5-8 yrs, without AD related mutations) were given chronic intracerebroventricular (i.c.v.) injections of FA or vehicle over a 12-month period. Monkeys were monitored for changes in cognitive ability and evaluated post-mortem for common AD pathological markers.
Results: Monkeys injected with FA were found to have significant spatial working memory impairments. Histopathological analysis revealed the presence of amyloid-β+ neuritic-like plaques, neurofibrillary tangle-like formations, increased tau protein phosphorylation, neuronal loss and reactive gliosis in three memory (and AD) related brain areas (the hippocampus, entorhinal cortex and prefrontal cortex (PFC)) of monkeys receiving i.c.v. injections of FA. ELISA assays revealed that the amounts of pT181 and Aβ42 were markedly higher in the PFC and hippocampus of FA treated monkeys.
Conclusion: FA was found to induce major AD-like pathological markers and cognitive impairments in young rhesus monkeys independent of genetic predispositions. This suggests FA may play a significant role in the initiation and progression of the disease.
Export Options
About this article
Cite this article as:
Zhai Rongwei , Rizak Joshua , Zheng Na , He Xiaping , Li Zhenhui , Yin Yong , Su Tao , He Yingge , He Rongqiao , Ma Yuanye , Yang Meifeng *, Wang Zhengbo*, Hu Xintian *, Alzheimer's Disease-Like Pathologies and Cognitive Impairments Induced by Formaldehyde in Non-Human Primates, Current Alzheimer Research 2018; 15 (14) . https://dx.doi.org/10.2174/1567205015666180904150118
DOI https://dx.doi.org/10.2174/1567205015666180904150118 |
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
-
New Molecular Avenues in Parkinson ’ s Disease Therapy
Current Topics in Medicinal Chemistry The Recent Development of α<sub>7</sub> Nicotinic Acetylcholine Receptor (nAChR) Ligands as Therapeutic Candidates for the Treatment of Central Nervous System (CNS) Diseases
Current Pharmaceutical Design Differential Cued-Stroop Performance in Cognitively Asymptomatic Older Adults with Biomarker-Identified Risk for Alzheimer’s Disease: A Pilot Study
Current Alzheimer Research Mitochondrial Toxins in Basal Ganglia Disorders: From Animal Models to Therapeutic Strategies
Current Neuropharmacology An Increase in Aβ42 in the Prefrontal Cortex is Associated with a Reversal-Learning Impairment in Alzheimers Disease Model Tg2576 APPsw Mice
Current Alzheimer Research The Heart and Brain Imaging in Lone Atrial Fibrillation – Are We Surprised?
Current Pharmaceutical Design Identification of a Missense Mutation in the α-galactosidase A Gene in a Chinese Family with Fabry Disease
Current Genomics Polymeric Materials and Formulation Technologies for Modified-Release Tablet Development
Mini-Reviews in Medicinal Chemistry Development of Bivalent Acetylcholinesterase Inhibitors as Potential Therapeutic Drugs for Alzheimers Disease
Current Pharmaceutical Design Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice
Current Alzheimer Research Histamine H4 Receptor: A Novel Target for Inflammation Therapy
Mini-Reviews in Medicinal Chemistry Assessment of the Aggregation Propensity of the β -amyloid Peptide During the Synthesis and when Free in Solution
Protein & Peptide Letters Implications of Epigenetic Mechanisms and their Targets in Cerebral Ischemia Models
Current Neuropharmacology Histamine and Histamine Receptor Antagonists in Cancer Biology
Inflammation & Allergy - Drug Targets (Discontinued) Natural Products as Anti-glycation Agents: Possible Therapeutic Potential for Diabetic Complications
Current Diabetes Reviews Dementia and the Default Mode
Current Alzheimer Research Synthesis of Novel 4-(Dimethylaminoalkyl)piperazine-1-carbodithioa t e Derivatives as Cholinesterase Inhibitors
Letters in Drug Design & Discovery Advantages of Nanotechnology- Based Chinese Herb Drugs on Biological Activities
Current Drug Metabolism Mediterranean Diet, Brain and Muscle: Olive Polyphenols and Resveratrol Protection in Neurodegenerative and Neuromuscular Disorders
Current Medicinal Chemistry Phosphodiesterase Inhibitors for Cognitive Enhancement
Current Pharmaceutical Design