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      SOMAscan-based proteomic measurements of plasma brain natriuretic peptide are decreased in mild cognitive impairment and in Alzheimer's dementia patients

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          Abstract

          Alzheimer's disease represents the most common age-related neurodegenerative disorder and a leading cause of progressive cognitive impairment. Predicting cognitive decline is challenging but would be invaluable in an increasingly aging population which also experiences a rising cardiovascular risk. In order to examine whether plasma measurements of one of the established biomarkers of heart failure, brain natriuretic peptide (BNP), reflect a decline in cognitive function, associated with Alzheimer's disease neurodegeneration, BNP levels were analysed, by using a novel assay called a SOMAscan, in 1. cognitively healthy, control subjects; 2. subjects with mild cognitive impairment, and 3. subjects with Alzheimer's disease. The results of our study show that the levels of the BNP were significantly different between the three types of diagnoses ( p < 0.05), whereby subjects with mild cognitive impairment had the lowest mean BNP value, and healthy subjects had the highest BNP value. Importantly, our results show that the levels of the BNP are influenced by the presence of at least one APOE4 allele in the healthy ( p < 0.05) and in the Alzheimer's disease groups of subjects ( p < 0.1). As the levels of the BNP appear to be independent of the APOE4 genotype in subjects with mild cognitive impairment, the results of our study support inclusion of measurements of plasma levels of the BNP in the list of the core Alzheimer's disease biomarkers for identification of the mild cognitive impairment group of patients. In addition, the results of our study warrant further investigations into molecular links between Alzheimer's disease-type cognitive decline and cardiovascular disorders.

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          Most cited references43

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          The diagnosis and management of mild cognitive impairment: a clinical review.

          Cognitive decline is a common and feared aspect of aging. Mild cognitive impairment (MCI) is defined as the symptomatic predementia stage on the continuum of cognitive decline, characterized by objective impairment in cognition that is not severe enough to require help with usual activities of daily living.
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            2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure.

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              Age, APOE and sex: Triad of risk of Alzheimer's disease.

              Age, apolipoprotein E ε4 (APOE) and chromosomal sex are well-established risk factors for late-onset Alzheimer's disease (LOAD; AD). Over 60% of persons with AD harbor at least one APOE-ε4 allele. The sex-based prevalence of AD is well documented with over 60% of persons with AD being female. Evidence indicates that the APOE-ε4 risk for AD is greater in women than men, which is particularly evident in heterozygous women carrying one APOE-ε4 allele. Paradoxically, men homozygous for APOE-ε4 are reported to be at greater risk for mild cognitive impairment and AD. Herein, we discuss the complex interplay between the three greatest risk factors for Alzheimer's disease, age, APOE-ε4 genotype and chromosomal sex. We propose that the convergence of these three risk factors, and specifically the bioenergetic aging perimenopause to menopause transition unique to the female, creates a risk profile for AD unique to the female. Further, we discuss the specific risk of the APOE-ε4 positive male which appears to emerge early in the aging process. Evidence for impact of the triad of AD risk factors is most evident in the temporal trajectory of AD progression and burden of pathology in relation to APOE genotype, age and sex. Collectively, the data indicate complex interactions between age, APOE genotype and gender that belies a one size fits all approach and argues for a precision medicine approach that integrates across the three main risk factors for Alzheimer's disease.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: ResourcesRole: SoftwareRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: ResourcesRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 February 2019
                2019
                : 14
                : 2
                : e0212261
                Affiliations
                [1 ] Department of Pharmacology, Sarajevo Medical School, Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina
                [2 ] Department of Cardiology, General Hospital "Prim.Dr. Abdulah Nakas", Sarajevo, Bosnia and Herzegovina
                [3 ] Computer Science and Information Systems Department, Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina
                [4 ] Department of Pediatric Cardiology, University Clinical Center, Sarajevo, Bosnia and Herzegovina
                Universitatsklinikum Leipzig, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3410-7079
                http://orcid.org/0000-0002-8205-0137
                http://orcid.org/0000-0002-6099-6415
                Article
                PONE-D-18-26013
                10.1371/journal.pone.0212261
                6375605
                30763368
                97fb212f-a65e-4635-9cee-96975b000ab3
                © 2019 Begic et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 September 2018
                : 30 January 2019
                Page count
                Figures: 4, Tables: 1, Pages: 14
                Funding
                The authors received no funding for the work presented in this study. However, the authors used the AddNeuroMed data that have been obtained through a public-private partnership supported by EFPIA companies and SMEs as part of InnoMed (Innovative Medicines in Europe), an Integrated Project funded by the European Union of the Sixth Framework program priority FP6-2004-LIFESCIHEALTH-5, which was awarded to the clinical leads, who were responsible for data collection - Iwona Kloszewska (Lodz), Simon Lovestone (London), Patrizia Mecocci (Perugia), Hilkka Soininen (Kuopio), Magda Tsolaki (Thessaloniki), and Bruno Vellas (Toulouse), imaging leads - Andy Simmons (London), Lars-Olof Wahlund (Stockholm) and Christian Spenger (Zurich), and bioinformatics leads - Richard Dobson (London) and Stephen Newhouse (London). The authors have obtained authorised access to the AddNeuroMed data from the Sage Bionetworks Access and Compliance Team ( https://www.synapse.org/#!Synapse:syn2790911/wiki/235389).
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Dementia
                Alzheimer's Disease
                Medicine and Health Sciences
                Neurology
                Dementia
                Alzheimer's Disease
                Medicine and Health Sciences
                Neurology
                Neurodegenerative Diseases
                Alzheimer's Disease
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Blood
                Blood Plasma
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Natriuretic Peptide
                Brain Natriuretic Peptide
                Medicine and Health Sciences
                Diagnostic Medicine
                Alzheimer's Disease Diagnosis and Management
                Medicine and Health Sciences
                Cardiology
                Heart Failure
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Computer and Information Sciences
                Software Engineering
                Preprocessing
                Engineering and Technology
                Software Engineering
                Preprocessing
                Custom metadata
                This dataset can be accessed by its DOI number which is as follows - doi: 10.7303/syn17021321, or it can be accessed from the Synapse-Sage Bionetworks Data Platform under the following URL - https://www.synapse.org/#!Synapse:syn17021321.

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