Abstract
The APOE genotype is a known susceptibility factor for Alzheimer’s disease (AD). It is apparent that the presence of the APOE ε40 allele increases the risk for developing AD, lowers the age of onset in AD, and may influence the pathological burden seen in AD. In this study, we asked whether BACE1 levels differ by APOE genotype in the AD and non-demented (ND) brain. We isolated mid-frontal cortex (MFC) and mid-temporal cortex (MTC) from post-mortem ND and AD subjects that were APOE ε3/3, ε3/4, ε4/4 carriers. All AD subjects met NINDS-ADRDA and NIA-Reagan criteria for a diagnosis of AD. The MFC and MTC were homogenized and the lysates underwent ELISA and Western blotting for BACE1. The ELISA revealed that total BACE1 levels were lower in the MFC of AD compared to ND subjects. Furthermore, in APOE ε4 carriers BACE1 levels were lower than ε3/3 carriers in the ND frontal cortex. No difference in BACE1 levels was observed in AD MFC and in ND and AD MTC tissues. The ELISA results were confirmed by Western blotting. Our data suggest that brain BACEl levels may be influenced by the apolipoprotein E genotype before the onset of AD, providing an alternative explanation for the lower amyloid beta 42 levels in CSF in ND and AD subjects.
Keywords: Alzheimer’s disease, APOE, BACE1, brain, ELISA, frontal cortex
Current Alzheimer Research
Title:BACE1 Levels by APOE Genotype in Non-Demented and Alzheimer’s Post-Mortem Brains
Volume: 10 Issue: 3
Author(s): Boris Decourt, Amanda Gonzales, Thomas G. Beach, Michael Malek-Ahmadi, Aaron Walker, Lucia Sue, Douglas G. Walker and Marwan N. Sabbagh
Affiliation:
Keywords: Alzheimer’s disease, APOE, BACE1, brain, ELISA, frontal cortex
Abstract: The APOE genotype is a known susceptibility factor for Alzheimer’s disease (AD). It is apparent that the presence of the APOE ε40 allele increases the risk for developing AD, lowers the age of onset in AD, and may influence the pathological burden seen in AD. In this study, we asked whether BACE1 levels differ by APOE genotype in the AD and non-demented (ND) brain. We isolated mid-frontal cortex (MFC) and mid-temporal cortex (MTC) from post-mortem ND and AD subjects that were APOE ε3/3, ε3/4, ε4/4 carriers. All AD subjects met NINDS-ADRDA and NIA-Reagan criteria for a diagnosis of AD. The MFC and MTC were homogenized and the lysates underwent ELISA and Western blotting for BACE1. The ELISA revealed that total BACE1 levels were lower in the MFC of AD compared to ND subjects. Furthermore, in APOE ε4 carriers BACE1 levels were lower than ε3/3 carriers in the ND frontal cortex. No difference in BACE1 levels was observed in AD MFC and in ND and AD MTC tissues. The ELISA results were confirmed by Western blotting. Our data suggest that brain BACEl levels may be influenced by the apolipoprotein E genotype before the onset of AD, providing an alternative explanation for the lower amyloid beta 42 levels in CSF in ND and AD subjects.
Export Options
About this article
Cite this article as:
Decourt Boris, Gonzales Amanda, G. Beach Thomas, Malek-Ahmadi Michael, Walker Aaron, Sue Lucia, G. Walker Douglas and N. Sabbagh Marwan, BACE1 Levels by APOE Genotype in Non-Demented and Alzheimer’s Post-Mortem Brains, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030010
DOI https://dx.doi.org/10.2174/1567205011310030010 |
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
-
Safety and Efficacy of Duloxetine in the Treatment of Diabetic Peripheral Neuropathic Pain in Older Patients
Current Drug Safety Editorial: In Silico Studies in Drug Research Against Neurodegenerative Diseases
Current Neuropharmacology Clinical Potential of Yi-Gan San (Yokukansan) for the Treatment of Psychiatric Disorders
Current Psychiatry Reviews Hybrid PET Imaging in Neurologic Disease: PET/MRI Rather than PET/CT
Current Medical Imaging Growth Factors and Astrocytes Metabolism: Possible Roles for Platelet Derived Growth Factor
Medicinal Chemistry Mass Spectrometry Techniques: Principles and Practices for Quantitative Proteomics
Current Protein & Peptide Science Editorial [Hot Topic: Auditory Processing Disorder (Guest Editors: Vasiliki Maria Iliadou)]
Current Pediatric Reviews An Overview of Piperazine Scaffold as Promising Nucleus for Different Therapeutic Targets
Current Pharmaceutical Design Use of STAT1 Inhibitors in the Treatment of Brain I/R Injury and Neurodegenerative Diseases
Central Nervous System Agents in Medicinal Chemistry Stroke as a Consequence of Sleep Apnea: Epidemiology, Pathophysiology and Treatment Strategies
Current Respiratory Medicine Reviews Humanized Mouse Models of HIV-1 Latency
Current HIV Research Folate Status and Depressive Symptoms in Reproductive-Age Women
Current Nutrition & Food Science Adenosine Neuromodulation and Traumatic Brain Injury
Current Neuropharmacology Uric Acid and Cu/Zn Superoxide Dismutase: Potential Strategies and Biomarkers in Functional Recovery of Post-Acute Ischemic Stroke Patients after Intensive Neurorehabilitation
Current Neurovascular Research Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets A Link Between Brain Insulin Resistance and Cognitive Dysfunctions: Targeting Ca2+/cAMP Signalling
Central Nervous System Agents in Medicinal Chemistry Deep Learning: A Breakthrough in Medical Imaging
Current Medical Imaging Mitochondria as a Therapeutic Target in Alzheimers Disease and Diabetes
CNS & Neurological Disorders - Drug Targets Interferon gama induced Tryptophan Degradation Neuropsychiatric and Immunological Consequences
Current Drug Metabolism Editorial - Progress of Current Alzheimer Research
Current Alzheimer Research