Abstract
Alzheimer’s disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify individuals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD individuals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.
Keywords: Alzheimer's disease, amyloid, buccal cells, DNA content, laser scanning cytometry, mild cognitive impairment, neutral lipids.
Current Alzheimer Research
Title:High Content, Multi-Parameter Analyses in Buccal Cells to Identify Alzheimer’s Disease
Volume: 13 Issue: 7
Author(s): Maxime François, Michael F. Fenech, Philip Thomas, Maryam Hor, Alan Rembach, Ralph N. Martins, Stephanie R. Rainey-Smith, Colin L. Masters, David Ames, Christopher C. Rowe, S. Lance Macaulay, Andrew F. Hill, Wayne R. Leifert and The Australian Imaging, Biomarkers and Lifestyle Study Research Group
Affiliation:
Keywords: Alzheimer's disease, amyloid, buccal cells, DNA content, laser scanning cytometry, mild cognitive impairment, neutral lipids.
Abstract: Alzheimer’s disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify individuals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD individuals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.
Export Options
About this article
Cite this article as:
François Maxime, F. Fenech Michael, Thomas Philip, Hor Maryam, Rembach Alan, N. Martins Ralph, R. Rainey-Smith Stephanie, L. Masters Colin, Ames David, C. Rowe Christopher, Lance Macaulay S., F. Hill Andrew, R. Leifert Wayne and The Australian Imaging, Biomarkers and Lifestyle Study Research Group , High Content, Multi-Parameter Analyses in Buccal Cells to Identify Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (7) . https://dx.doi.org/10.2174/1567205013666160315112151
DOI https://dx.doi.org/10.2174/1567205013666160315112151 |
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
-
Severe Psychiatric Disorders in Mid-Life and Risk of Dementia in Late- Life (Age 65-84 Years): A Population Based Case-Control Study
Current Alzheimer Research Imaging as a Strategy for Premortem Diagnosis and Staging of Tauopathies
Current Alzheimer Research Sleep-Disordered Breathing and Cardiovascular Disease: Exploring Pathophysiology and Existing Data
Current Respiratory Medicine Reviews A Feature-Free 30-Disease Pathological Brain Detection System by Linear Regression Classifier
CNS & Neurological Disorders - Drug Targets GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients
Current Hypertension Reviews Significance of Prion and Prion-Like Proteins in Cancer Development, Progression and Multi-Drug Resistance
Current Cancer Drug Targets Editorial (Thematic Issue: Regulating the CNS Grand Regulator; N-methyl-D-aspartate Receptor-Mediated Neurotransmission)
Current Pharmaceutical Design Cardiovascular Toxicity of Cyclooxygenase Inhibitors and Promising Natur a l Substitutes
Current Pharmaceutical Design Intravitreal Bevacizumab (Avastin®) for Diabetic Retinopathy at 24-months: The 2008 Juan Verdaguer-Planas Lecture
Current Diabetes Reviews Molecular Hydrogen as a Neuroprotective Agent
Current Neuropharmacology Meet Our Section Editor:
Current Pharmaceutical Biotechnology Serotonin Receptor Binding Characteristics of Geissoschizine Methyl Ether, an Indole Alkaloid in Uncaria Hook
Current Medicinal Chemistry Prevalence of Neuropsychiatric Symptoms in Alzheimers Disease and Vascular Dementia
Current Alzheimer Research Effects of Nicotine on the Cardiovascular System
Vascular Disease Prevention (Discontinued) Increased Acetylation of Histone H4 at Lysine 12 (H4K12) in Monocytes of Transgenic Alzheimer’s Mice and in Human Patients
Current Alzheimer Research Transthyretin Decrease in Plasma of MCI and AD Patients: Investigation of Mechanisms for Disease Modulation
Current Alzheimer Research Heterogeneity in Cost-Effectiveness Analysis of Vaccination for Mild and Moderate Alzheimer’s Disease
Current Alzheimer Research History and Therapeutic Use of MAO-A Inhibitors: A Historical Perspective of MAO-A Inhibitors As Antidepressant Drug
Current Topics in Medicinal Chemistry Choline Alphoscerate (Alpha-Glyceryl-Phosphoryl-Choline) An Old Choline- containing Phospholipid with a Still Interesting Profile As Cognition Enhancing Agent
Current Alzheimer Research Evidence for the Role of Luteinizing Hormone in Alzheimer Disease
Endocrine, Metabolic & Immune Disorders - Drug Targets