TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease

Over the last few years, intense research efforts have been made to anticipate or improve the diagnosis of Alzheimer’s disease by detecting blood biomarkers. However, the most promising blood biomarkers identified to date have some limitations, most of them related to the techniques required for the...

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Main Authors: Paloma Aivar, Carolina Bianchi, Caterina Di Lauro, Lucia Soria-Tobar, Beatriz Alvarez-Castelao, Miguel Calero, Miguel Medina, Miguel Diaz-Hernandez
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/10897
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author Paloma Aivar
Carolina Bianchi
Caterina Di Lauro
Lucia Soria-Tobar
Beatriz Alvarez-Castelao
Miguel Calero
Miguel Medina
Miguel Diaz-Hernandez
author_facet Paloma Aivar
Carolina Bianchi
Caterina Di Lauro
Lucia Soria-Tobar
Beatriz Alvarez-Castelao
Miguel Calero
Miguel Medina
Miguel Diaz-Hernandez
author_sort Paloma Aivar
collection DOAJ
description Over the last few years, intense research efforts have been made to anticipate or improve the diagnosis of Alzheimer’s disease by detecting blood biomarkers. However, the most promising blood biomarkers identified to date have some limitations, most of them related to the techniques required for their detection. Hence, new blood biomarkers should be identified to improve the diagnosis of AD, better discriminate between AD and mild cognitive impairment (MCI) and identify cognitively unimpaired (CU) older individuals at risk for progression to AD. Our previous studies demonstrated that both the purinergic receptor P2X7 and the tissue-nonspecific alkaline phosphatase ectoenzyme (TNAP) are upregulated in the brains of AD patients. Since both proteins are also present in plasma, we investigated whether plasma P2X7R and TNAP are altered in MCI and AD patients and, if so, their potential role as AD biomarkers. We found that AD but not MCI patients present increased plasma P2X7R levels. Nevertheless, TNAP plasma activity was increased in MCI patients and decreased in the AD group. ROC curve analysis indicated that measuring both parameters has a reasonable discriminating capability to diagnose MCI and AD conditions. In addition to confirming that individuals progressing to MCI have increased TNAP activity in plasma, longitudinal studies also revealed that CU individuals have lower plasma TNAP activity than stable controls. Thus, we propose that P2X7 and TNAP could serve as new plasma biomarkers for MCI and AD.
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spelling doaj.art-d83ad796a8db480996e26c5806c0fc532023-11-18T16:45:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131089710.3390/ijms241310897TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s DiseasePaloma Aivar0Carolina Bianchi1Caterina Di Lauro2Lucia Soria-Tobar3Beatriz Alvarez-Castelao4Miguel Calero5Miguel Medina6Miguel Diaz-Hernandez7Departamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainCentro de Investigación Biomédica En Red-Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, SpainCentro de Investigación Biomédica En Red-Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, SpainOver the last few years, intense research efforts have been made to anticipate or improve the diagnosis of Alzheimer’s disease by detecting blood biomarkers. However, the most promising blood biomarkers identified to date have some limitations, most of them related to the techniques required for their detection. Hence, new blood biomarkers should be identified to improve the diagnosis of AD, better discriminate between AD and mild cognitive impairment (MCI) and identify cognitively unimpaired (CU) older individuals at risk for progression to AD. Our previous studies demonstrated that both the purinergic receptor P2X7 and the tissue-nonspecific alkaline phosphatase ectoenzyme (TNAP) are upregulated in the brains of AD patients. Since both proteins are also present in plasma, we investigated whether plasma P2X7R and TNAP are altered in MCI and AD patients and, if so, their potential role as AD biomarkers. We found that AD but not MCI patients present increased plasma P2X7R levels. Nevertheless, TNAP plasma activity was increased in MCI patients and decreased in the AD group. ROC curve analysis indicated that measuring both parameters has a reasonable discriminating capability to diagnose MCI and AD conditions. In addition to confirming that individuals progressing to MCI have increased TNAP activity in plasma, longitudinal studies also revealed that CU individuals have lower plasma TNAP activity than stable controls. Thus, we propose that P2X7 and TNAP could serve as new plasma biomarkers for MCI and AD.https://www.mdpi.com/1422-0067/24/13/10897P2X7RTNAPbiomarkerAlzheimer
spellingShingle Paloma Aivar
Carolina Bianchi
Caterina Di Lauro
Lucia Soria-Tobar
Beatriz Alvarez-Castelao
Miguel Calero
Miguel Medina
Miguel Diaz-Hernandez
TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease
International Journal of Molecular Sciences
P2X7R
TNAP
biomarker
Alzheimer
title TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease
title_full TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease
title_fullStr TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease
title_full_unstemmed TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease
title_short TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease
title_sort tnap and p2x7r new plasma biomarkers for alzheimer s disease
topic P2X7R
TNAP
biomarker
Alzheimer
url https://www.mdpi.com/1422-0067/24/13/10897
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