Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease is the most common type of dementia in the elderly. It is a progressive degenerative disorder that may begin to develop up to 15?years before clinical symptoms appear. The identification of early biomarkers is crucial to enable a prompt diagnosis and to start effective inter...

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Autores: Botello-Marabotto M, Martínez-Bisbal MC, Calero M, Bernardos A, Pastor AB, Medina M, Martínez-Máñez R
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Centro de Investigación Principe Felipe (CIPF)
Repositorio:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p4153
Acceso en línea:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4153
Access Level:acceso abierto
Palabra clave:Alzheimer's disease, Biomarkers, Metabolomics, Mild cognitive impairment, NMR spectroscopy
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spelling Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.Botello-Marabotto MMartínez-Bisbal MCCalero MBernardos APastor ABMedina MMartínez-Máñez RAlzheimer's disease, Biomarkers, Metabolomics, Mild cognitive impairment, NMR spectroscopyAlzheimer's disease is the most common type of dementia in the elderly. It is a progressive degenerative disorder that may begin to develop up to 15?years before clinical symptoms appear. The identification of early biomarkers is crucial to enable a prompt diagnosis and to start effective interventions. In this work, we conducted a metabolomic study using proton Nuclear Magnetic Resonance ( 1 H NMR) spectroscopy in serum samples from patients with neuropathologically confirmed Alzheimer's disease (AD, n?=?51), mild cognitive impairment (MCI, n?=?27), and cognitively healthy controls (HC, n?=?50) to search for metabolites that could be used as biomarkers. Patients and controls underwent yearly clinical follow-ups for up to six years. MCI group included samples from three subgroups of subjects with different disease progression rates. The first subgroup included subjects that remained clinically stable at the MCI stage during the period of study (stable MCI, S-MCI, n?=?9). The second subgroup accounted for subjects which were diagnosed with MCI at the moment of blood extraction, but progressed to clinical dementia in subsequent years (MCI-to-dementia, MCI-D, n?=?14). The last subgroup was composed of subjects that had been diagnosed as dementia for the first time at the moment of sample collection (incipient dementia, Incp-D, n?=?4). Partial Least Square Discriminant Analysis (PLS-DA) models were developed. Three models were obtained, one to discriminate between AD and HC samples with high sensitivity (93.75%) and specificity (94.75%), another model to discriminate between AD and MCI samples (100% sensitivity and 82.35% specificity), and a last model to discriminate HC and MCI with lower sensitivity and specificity (67% and 50%). Differences within the MCI group were further studied in an attempt to determine those MCI subjects that could develop AD-type dementia in the future. The relative concentration of metabolites, and metabolic pathways were studied. Alterations in the pathways of alanine, aspartate and glutamate metabolism, pantothenate and CoA biosynthesis, and beta-alanine metabolism, were found when HC and MCI- D patients were compared. In contrast, no pathway was found disturbed in the comparison of S-MCI with HC groups. These results highlight the potential of 1 H NMR metabolomics to support the diagnosis of dementia in a less invasive way, and set a starting point for the study of potential biomarkers to identify MCI or HC subjects at risk of developing AD in the future.ACADEMIC PRESS INC ELSEVIER SCIENCE2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4153NEUROBIOLOGY OF DISEASEISSN: 09699961ISSNe: 1095953Xreponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)instname:Centro de Investigación Principe Felipe (CIPF)Inglésinfo:eu-repo/semantics/openAccessoai:cipf.fundanetsuite.com:p41532026-06-17T11:19:47Z
dc.title.none.fl_str_mv Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
title Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
spellingShingle Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
Botello-Marabotto M
Alzheimer's disease, Biomarkers, Metabolomics, Mild cognitive impairment, NMR spectroscopy
title_short Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
title_full Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
title_fullStr Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
title_full_unstemmed Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
title_sort Non-invasive biomarkers for mild cognitive impairment and Alzheimer's disease.
dc.creator.none.fl_str_mv Botello-Marabotto M
Martínez-Bisbal MC
Calero M
Bernardos A
Pastor AB
Medina M
Martínez-Máñez R
author Botello-Marabotto M
author_facet Botello-Marabotto M
Martínez-Bisbal MC
Calero M
Bernardos A
Pastor AB
Medina M
Martínez-Máñez R
author_role author
author2 Martínez-Bisbal MC
Calero M
Bernardos A
Pastor AB
Medina M
Martínez-Máñez R
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer's disease, Biomarkers, Metabolomics, Mild cognitive impairment, NMR spectroscopy
topic Alzheimer's disease, Biomarkers, Metabolomics, Mild cognitive impairment, NMR spectroscopy
description Alzheimer's disease is the most common type of dementia in the elderly. It is a progressive degenerative disorder that may begin to develop up to 15?years before clinical symptoms appear. The identification of early biomarkers is crucial to enable a prompt diagnosis and to start effective interventions. In this work, we conducted a metabolomic study using proton Nuclear Magnetic Resonance ( 1 H NMR) spectroscopy in serum samples from patients with neuropathologically confirmed Alzheimer's disease (AD, n?=?51), mild cognitive impairment (MCI, n?=?27), and cognitively healthy controls (HC, n?=?50) to search for metabolites that could be used as biomarkers. Patients and controls underwent yearly clinical follow-ups for up to six years. MCI group included samples from three subgroups of subjects with different disease progression rates. The first subgroup included subjects that remained clinically stable at the MCI stage during the period of study (stable MCI, S-MCI, n?=?9). The second subgroup accounted for subjects which were diagnosed with MCI at the moment of blood extraction, but progressed to clinical dementia in subsequent years (MCI-to-dementia, MCI-D, n?=?14). The last subgroup was composed of subjects that had been diagnosed as dementia for the first time at the moment of sample collection (incipient dementia, Incp-D, n?=?4). Partial Least Square Discriminant Analysis (PLS-DA) models were developed. Three models were obtained, one to discriminate between AD and HC samples with high sensitivity (93.75%) and specificity (94.75%), another model to discriminate between AD and MCI samples (100% sensitivity and 82.35% specificity), and a last model to discriminate HC and MCI with lower sensitivity and specificity (67% and 50%). Differences within the MCI group were further studied in an attempt to determine those MCI subjects that could develop AD-type dementia in the future. The relative concentration of metabolites, and metabolic pathways were studied. Alterations in the pathways of alanine, aspartate and glutamate metabolism, pantothenate and CoA biosynthesis, and beta-alanine metabolism, were found when HC and MCI- D patients were compared. In contrast, no pathway was found disturbed in the comparison of S-MCI with HC groups. These results highlight the potential of 1 H NMR metabolomics to support the diagnosis of dementia in a less invasive way, and set a starting point for the study of potential biomarkers to identify MCI or HC subjects at risk of developing AD in the future.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4153
url https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4153
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ACADEMIC PRESS INC ELSEVIER SCIENCE
publisher.none.fl_str_mv ACADEMIC PRESS INC ELSEVIER SCIENCE
dc.source.none.fl_str_mv NEUROBIOLOGY OF DISEASE
ISSN: 09699961
ISSNe: 1095953X
reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname:Centro de Investigación Principe Felipe (CIPF)
instname_str Centro de Investigación Principe Felipe (CIPF)
reponame_str r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
collection r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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