Abstract
Objective: Postmortem and genetic studies of clinically diagnosed Frontotemporal dementia (FTD) patients suggest that a number of clinically diagnosed FTD patients are actually "frontal variants" of Alzheimer's disease (fvAD). The purpose of this study was to evaluate this hypothesis by combining neuropathological data, genetic association studies of APOE, phenotype-APOE genotype correlations and discriminant analysis techniques. Methods: Neuropathological information on 24 FTD cases, genetic association studies of APOE (168 FTD, 3083 controls and 2528 AD), phenotypegenotype correlations and discriminant techniques (LDA, logistic regression and decision trees) were combined to identify fvAD patients within a clinical FTD series. Results: Four of 24 FTLD patients (16.6%) met criteria for definite AD. By comparing allele and genotype frequencies of APOE in controls, FTD and AD groups and by applying the Hardy- Weinberg equilibrium law (HWE), we inferred a consistent (17.2%) degree of AD contamination in clinical FTD. A penetrance analysis for APOE 4 genotype in the FTD series identified 14 features for discrimination analysis. These features were compared between clinical AD (n=332) and clinical FTD series (n=168) and classifiers were constructed usinglinear discriminant analysis logistic regression or decision tree techniques. The classifier had 92.8% sensitivity to FTD and 93.4% sensitivity to AD relative to neuropathology (global AUC=0.939, p<<0.001). We identified 30 potential fvAD cases (17.85%) in the clinical FTD sample. Conclusion: The APOE locus association in clinical FTD might be entirely explained by the existence of "hidden" fvAD cases within an FTD sample. The degree of fvAD contamination can be inferred from APOE genotypes.
Keywords: Alzheimer's disease, apolipoprotein E4, diagnostic classification, frontotemporal lobe dementia, genetics.
Current Alzheimer Research
Title:Identification of Misdiagnosed Fronto-Temporal Dementia using APOE Genotype and Phenotype-Genotype Correlation Analyses
Volume: 11 Issue: 2
Author(s): Isabel Hernandez, Ana Mauleon, Maitee Rosense-Roca, Montserrat Alegret, Georgina Vinyes, Anna Espinosa, Oscar Sotolongo-Grau, James T. Becker, Sergi Valero, Lluís Tarraga, Oscar L. Lopez, Agustín Ruiz and Merce Boada
Affiliation:
Keywords: Alzheimer's disease, apolipoprotein E4, diagnostic classification, frontotemporal lobe dementia, genetics.
Abstract: Objective: Postmortem and genetic studies of clinically diagnosed Frontotemporal dementia (FTD) patients suggest that a number of clinically diagnosed FTD patients are actually "frontal variants" of Alzheimer's disease (fvAD). The purpose of this study was to evaluate this hypothesis by combining neuropathological data, genetic association studies of APOE, phenotype-APOE genotype correlations and discriminant analysis techniques. Methods: Neuropathological information on 24 FTD cases, genetic association studies of APOE (168 FTD, 3083 controls and 2528 AD), phenotypegenotype correlations and discriminant techniques (LDA, logistic regression and decision trees) were combined to identify fvAD patients within a clinical FTD series. Results: Four of 24 FTLD patients (16.6%) met criteria for definite AD. By comparing allele and genotype frequencies of APOE in controls, FTD and AD groups and by applying the Hardy- Weinberg equilibrium law (HWE), we inferred a consistent (17.2%) degree of AD contamination in clinical FTD. A penetrance analysis for APOE 4 genotype in the FTD series identified 14 features for discrimination analysis. These features were compared between clinical AD (n=332) and clinical FTD series (n=168) and classifiers were constructed usinglinear discriminant analysis logistic regression or decision tree techniques. The classifier had 92.8% sensitivity to FTD and 93.4% sensitivity to AD relative to neuropathology (global AUC=0.939, p<<0.001). We identified 30 potential fvAD cases (17.85%) in the clinical FTD sample. Conclusion: The APOE locus association in clinical FTD might be entirely explained by the existence of "hidden" fvAD cases within an FTD sample. The degree of fvAD contamination can be inferred from APOE genotypes.
Export Options
About this article
Cite this article as:
Hernandez Isabel, Mauleon Ana, Rosense-Roca Maitee, Alegret Montserrat, Vinyes Georgina, Espinosa Anna, Sotolongo-Grau Oscar, Becker T. James, Valero Sergi, Tarraga Lluís, Lopez L. Oscar, Ruiz Agustín and Boada Merce, Identification of Misdiagnosed Fronto-Temporal Dementia using APOE Genotype and Phenotype-Genotype Correlation Analyses, Current Alzheimer Research 2014; 11 (2) . https://dx.doi.org/10.2174/1567205010666131212120443
DOI https://dx.doi.org/10.2174/1567205010666131212120443 |
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
-
Central Nervous System Manifestations in Systemic Lupus Erythematosus
Current Rheumatology Reviews Dynamic Role of Macrophage Sub Types on Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy
Cardiovascular & Hematological Agents in Medicinal Chemistry Glutamate Receptors in Human Caudate Nucleus in Normal Aging and Alzheimer’s Disease
Current Alzheimer Research Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis <i>In Vitro</i>
CNS & Neurological Disorders - Drug Targets Clinical Significance of the Cardio-Ankle Vascular Index (CAVI) in Hypertension
Current Hypertension Reviews Impact of Patient Knowledge of Hypertension Complications on Adherence to Antihypertensive Therapy
Current Hypertension Reviews Angiogenesis-regulating microRNAs and Ischemic Stroke
Current Vascular Pharmacology Schizophrenia: Causes and Treatments
Current Pharmaceutical Design “SLY AS A FOXO”: New Paths with Forkhead Signaling in the Brain
Current Neurovascular Research Perspectives on Brain-Targeting Drug Delivery Systems
Current Pharmaceutical Biotechnology Chronic Administration of an Aglycosylated Murine Antibody of Ponezumab Does Not Worsen Microhemorrhages in Aged Tg2576 Mice
Current Alzheimer Research Astrocyte`s RAGE: More Than Just a Question of Mood
Central Nervous System Agents in Medicinal Chemistry Impact of Alzheimers Disease on the Functional Connectivity of Spontaneous Brain Activity
Current Alzheimer Research The Aging of the Adaptive Immune System
Current Immunology Reviews (Discontinued) BACE1 Levels by APOE Genotype in Non-Demented and Alzheimer’s Post-Mortem Brains
Current Alzheimer Research Regulation and Function of DNA and Histone Methylations
Current Pharmaceutical Design Pomegranate Extract Modulates Processing of Amyloid-β Precursor Protein in an Aged Alzheimer`s Disease Animal Model
Current Alzheimer Research Diagnosis and Management of Hypertensive Emergencies Complicating Pregnancy
Current Women`s Health Reviews Views on Amyloid Hypothesis and Secretase Inhibitors for Treating Alzheimers Disease: Progress and Problems
Current Pharmaceutical Design The Panomics Approach in Neurodegenerative Disorders
Current Medicinal Chemistry