Abstract
Context: Alzheimer’s disease (AD) is usually only diagnosed many years after pathology begins. Earlier detection would allow emerging interventions to have a greater chance to preserve healthy brain function. A rare form of Alzheimer’s disease, caused by autosomal-dominant mutations, affects carriers with 100% certainty and at a younger age specific to their mutation. Studying families with these mutations allows a unique investigation of the temporal sequence of biomarker changes in Alzheimer’s disease.
Objective: To determine whether the pupil flash response (PFR), previously reported to be altered in sporadic Alzheimer’s disease, is different in pre-symptomatic mutation carriers.
Design: Researchers blinded to participant mutation status collected pupil response data from cognitively normal participants in the Dominantly Inherited Alzheimer's Network (DIAN) Study during 2010-2011.
Setting: The pupil response was examined at the McCusker Alzheimer’s Research Foundation in Perth, Western Australia.
Participants: Participants were from a single family harboring an Amyloid-Beta Precursor Protein genetic mutation (APPGlu693Gln). Six carriers and six non-carriers were available for pupil testing (age 43.0±8.3 years old, 2 males and 10 females, 4 with hypertension).
Main Outcome Measure: Pupil response parameter comparison between mutation carriers and non-carriers.
Results: 75% recovery time was longer in mutation carriers (p<0.0003, ROC AUC 1.000, Sensitivity 100%, Specificity 100%) and percentage recovery 3.5 seconds after stimulus was less in mutation carriers (p<0.006, ROC AUC 1.000, Sensitivity 100%, Specificity 100%).
Conclusions: PFR changes occur pre-symptomatically in autosomal dominant AD mutation carriers, supporting further investigation of PFR for early detection of AD.
Keywords: Alzheimer’s, autosomal, amyloid, eye, pupil.
Current Alzheimer Research
Title:Pupil Response Biomarkers Distinguish Amyloid Precursor Protein Mutation Carriers from Non-Carriers
Volume: 10 Issue: 8
Author(s): Shaun M. Frost, Yogesan Kanagasingam, Hamid R. Sohrabi, Kevin Taddei, Randall Bateman, John Morris, Tammie Benzinger, Alison Goate, Colin L. Masters and Ralph N. Martins
Affiliation:
Keywords: Alzheimer’s, autosomal, amyloid, eye, pupil.
Abstract: Context: Alzheimer’s disease (AD) is usually only diagnosed many years after pathology begins. Earlier detection would allow emerging interventions to have a greater chance to preserve healthy brain function. A rare form of Alzheimer’s disease, caused by autosomal-dominant mutations, affects carriers with 100% certainty and at a younger age specific to their mutation. Studying families with these mutations allows a unique investigation of the temporal sequence of biomarker changes in Alzheimer’s disease.
Objective: To determine whether the pupil flash response (PFR), previously reported to be altered in sporadic Alzheimer’s disease, is different in pre-symptomatic mutation carriers.
Design: Researchers blinded to participant mutation status collected pupil response data from cognitively normal participants in the Dominantly Inherited Alzheimer's Network (DIAN) Study during 2010-2011.
Setting: The pupil response was examined at the McCusker Alzheimer’s Research Foundation in Perth, Western Australia.
Participants: Participants were from a single family harboring an Amyloid-Beta Precursor Protein genetic mutation (APPGlu693Gln). Six carriers and six non-carriers were available for pupil testing (age 43.0±8.3 years old, 2 males and 10 females, 4 with hypertension).
Main Outcome Measure: Pupil response parameter comparison between mutation carriers and non-carriers.
Results: 75% recovery time was longer in mutation carriers (p<0.0003, ROC AUC 1.000, Sensitivity 100%, Specificity 100%) and percentage recovery 3.5 seconds after stimulus was less in mutation carriers (p<0.006, ROC AUC 1.000, Sensitivity 100%, Specificity 100%).
Conclusions: PFR changes occur pre-symptomatically in autosomal dominant AD mutation carriers, supporting further investigation of PFR for early detection of AD.
Export Options
About this article
Cite this article as:
Frost M. Shaun, Kanagasingam Yogesan, Sohrabi R. Hamid, Taddei Kevin, Bateman Randall, Morris John, Benzinger Tammie, Goate Alison, Masters L. Colin and Martins N. Ralph, Pupil Response Biomarkers Distinguish Amyloid Precursor Protein Mutation Carriers from Non-Carriers, Current Alzheimer Research 2013; 10 (8) . https://dx.doi.org/10.2174/15672050113109990154
DOI https://dx.doi.org/10.2174/15672050113109990154 |
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
-
Haptoglobin Phenotype Correlates with the Extent of Cerebral Deep White Matter Lesions in Hypertensive Patients
Current Neurovascular Research Biomarkers of Atrial Fibrillation in Metabolic Syndrome
Current Medicinal Chemistry Myocardial Structure and Matrix Metalloproteinases
Current Topics in Medicinal Chemistry Preterm Birth and the Risk of Neurodevelopmental Disorders - Is There a Role for Epigenetic Dysregulation?
Current Genomics Air Pollution Exposure and Blood Pressure: An Updated Review of the Literature
Current Pharmaceutical Design CYP3A4 *1B Gene Polymorphism in Coronary Artery Disease Patients with Obesity Undergoing Statin Treatment
Current Pharmacogenomics and Personalized Medicine Diabetic Heart and the Cardiovascular Surgeon
Cardiovascular & Hematological Disorders-Drug Targets Clinical Review of COVID-19; Pathogenesis, Diagnosis, and Management
Current Pharmaceutical Design Preface
Current Pharmaceutical Design Medical Management of the Diabetic Patient with Coronary Artery Disease
Current Pharmaceutical Design An Agathokakological Tale of Δ<sup>9</sup>-THC: Exploration of Possible Biological Targets
Current Drug Targets Millennium Nutrient N,N-Dimethylglycine (DMG) and its Effectiveness in Autism Spectrum Disorders
Current Medicinal Chemistry Targeting Inflammation in Primary Cardiovascular Prevention
Current Pharmaceutical Design Manual Thrombectomy During Primary Coronary Intervention in Acute Myocardial Infarction: A Brief Review
Reviews on Recent Clinical Trials CYP4 Enzymes As Potential Drug Targets: Focus on Enzyme Multiplicity, Inducers and Inhibitors, and Therapeutic Modulation of 20- Hydroxyeicosatetraenoic Acid (20-HETE) Synthase and Fatty Acid ω- Hydroxylase Activities
Current Topics in Medicinal Chemistry Diagnostic and Therapeutic Potentials of microRNAs in Heart Failure
Current Topics in Medicinal Chemistry Emerging Anti-inflammatory Therapies for Atherosclerosis
Current Pharmaceutical Design Molecular Mechanisms of Restenosis After Percutaneous Peripheral Angioplasty and Approach to Endovascular Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders Trophoblast Invasion: A Possible Link Between Implantation Deficiencies and Preeclampsia
Current Women`s Health Reviews Drugs for the Treatment of Hypercholesterolemia and their Benefits Beyond Cholesterol Lowering to Prevent Vascular Disease
Vascular Disease Prevention (Discontinued)