Abstract
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid-β (Aβ) plaque formation, tau pathology, neurodegeneration and inflammatory processes. Monocytes are involved in inflammation in AD and are recruited to the diseased brain. Recently it has been shown that aberrant epigenetic processes including acetylation are associated with the development of AD. The aim of the present study was to examine acetylation of histone H4 at lysine 12 (H4K12) in monocytes in two transgenic AD mouse models (the triple transgenic 3xTg and a model overexpressing amyloid-precursor protein APP with the Swedish-Dutch-Iowa mutations), and to compare with monocytes isolated from human patients with mild cognitive impairment (MCI) and AD. Methods: Mouse and human monocytes were selectively isolated with a positive (PluriSelect) respectively with a negative selection method (Miltenyi). Histones were extracted and acetylation of H4K12 was analyzed by a quantification fluorometric kit. Moreover, monocyte cytokine release was measured and cell death analyzed by FACS using incorporation of 7-AAD. Results: Our data show a significant increase of monocytic H4K12 acetylation in both transgenic AD mouse models early during development of the plaque deposition in the brain. In line with these data we found significantly elevated acetylation of H4K12 in human patients with MCI but not in patients with AD. Further we observed that the monocytes of AD mice and of AD patients were significantly more vulnerable to cell damage (as seen by 7-AAD incorporation in FACS analysis) and displayed an enhanced release of pro-inflammatory cytokines (MIP2 and TNFα). Conclusion: Our findings indicate that epigenetic changes in peripheral monocytes are an early event in AD-pathology. Thus H4K12 acetylation may be considered as a novel biomarker for early changes in AD development.
Keywords: Acetylation, Alzheimer’s disease, epigenetics, H4K12, histones, MCI, monocytes.
Current Alzheimer Research
Title:Increased Acetylation of Histone H4 at Lysine 12 (H4K12) in Monocytes of Transgenic Alzheimer’s Mice and in Human Patients
Volume: 12 Issue: 8
Author(s): Barbara Plagg, Daniela Ehrlich, Kathrin M. Kniewallner, Josef Marksteiner and Christian Humpel
Affiliation:
Keywords: Acetylation, Alzheimer’s disease, epigenetics, H4K12, histones, MCI, monocytes.
Abstract: Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid-β (Aβ) plaque formation, tau pathology, neurodegeneration and inflammatory processes. Monocytes are involved in inflammation in AD and are recruited to the diseased brain. Recently it has been shown that aberrant epigenetic processes including acetylation are associated with the development of AD. The aim of the present study was to examine acetylation of histone H4 at lysine 12 (H4K12) in monocytes in two transgenic AD mouse models (the triple transgenic 3xTg and a model overexpressing amyloid-precursor protein APP with the Swedish-Dutch-Iowa mutations), and to compare with monocytes isolated from human patients with mild cognitive impairment (MCI) and AD. Methods: Mouse and human monocytes were selectively isolated with a positive (PluriSelect) respectively with a negative selection method (Miltenyi). Histones were extracted and acetylation of H4K12 was analyzed by a quantification fluorometric kit. Moreover, monocyte cytokine release was measured and cell death analyzed by FACS using incorporation of 7-AAD. Results: Our data show a significant increase of monocytic H4K12 acetylation in both transgenic AD mouse models early during development of the plaque deposition in the brain. In line with these data we found significantly elevated acetylation of H4K12 in human patients with MCI but not in patients with AD. Further we observed that the monocytes of AD mice and of AD patients were significantly more vulnerable to cell damage (as seen by 7-AAD incorporation in FACS analysis) and displayed an enhanced release of pro-inflammatory cytokines (MIP2 and TNFα). Conclusion: Our findings indicate that epigenetic changes in peripheral monocytes are an early event in AD-pathology. Thus H4K12 acetylation may be considered as a novel biomarker for early changes in AD development.
Export Options
About this article
Cite this article as:
Plagg Barbara, Ehrlich Daniela, Kniewallner M. Kathrin, Marksteiner Josef and Humpel Christian, Increased Acetylation of Histone H4 at Lysine 12 (H4K12) in Monocytes of Transgenic Alzheimer’s Mice and in Human Patients, Current Alzheimer Research 2015; 12 (8) . https://dx.doi.org/10.2174/1567205012666150710114256
DOI https://dx.doi.org/10.2174/1567205012666150710114256 |
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
-
Neurotransmitter Dysfunction and Neurotransmitter Replacement Therapy as Part of Frontotemporal Dementia Treatment
Current Psychiatry Reviews On the Physiological Relevance of Muscarinic Acetylcholine Receptors in Alzheimers Disease
Current Medicinal Chemistry Ameliorative Effect of Phosphodiesterase-5 Inhibitor in Rat Model of Vascular Dementia
Current Neurovascular Research Novel Systemic Markers for Patients with Alzheimer Disease? – A Pilot Study
Current Alzheimer Research Tuberculostatic Drugs Targeting Infections of the Central Nervous System
Anti-Infective Agents Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology
Current Alzheimer Research Pharmacological Countermeasures for the Acute Radiation Syndrome
Current Molecular Pharmacology Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies
Current Drug Targets Diabetic Cognitive Dysfunction: From Bench to Clinic
Current Medicinal Chemistry Imaging Amyloid Pathology in the Living Brain
Current Medical Imaging Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia
Central Nervous System Agents in Medicinal Chemistry Hypertension in Pregnancy: Pathophysiology & Management Strategies
Current Pharmaceutical Design Chemical and Pharmacological Aspects of Heteroaryl-Nitrones
Current Medicinal Chemistry Small Molecule Natural Products and Alzheimer’s Disease
Current Topics in Medicinal Chemistry Phenylbutyric Acid Protects Against Spatial Memory Deficits in a Model of Repeated Electroconvulsive Therapy
Current Neurovascular Research Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice
Current Alzheimer Research The Innate Immunity in Alzheimer Disease- Relevance to Pathogenesis and Therapy
Current Pharmaceutical Design Patent Annotations
Recent Patents on Anti-Infective Drug Discovery Histone Deacetylase Inhibitors: A Novel Therapeutic Approach to Huntingtons Disease (Complex Mechanism of Neuronal Death).
Current Alzheimer Research Neuroprotection Abilities of Cytosolic Phospholipase A2 Inhibitors in Kainic acid-induced Neurodegeneration
Current Drug Targets - Cardiovascular & Hematological Disorders