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...
Main Authors: | , , , , , , , |
---|---|
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 |
_version_ | 1797591586218967040 |
---|---|
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. |
first_indexed | 2024-03-11T01:39:28Z |
format | Article |
id | doaj.art-d83ad796a8db480996e26c5806c0fc53 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-11T01:39:28Z |
publishDate | 2023-06-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT palomaaivar tnapandp2x7rnewplasmabiomarkersforalzheimersdisease AT carolinabianchi tnapandp2x7rnewplasmabiomarkersforalzheimersdisease AT caterinadilauro tnapandp2x7rnewplasmabiomarkersforalzheimersdisease AT luciasoriatobar tnapandp2x7rnewplasmabiomarkersforalzheimersdisease AT beatrizalvarezcastelao tnapandp2x7rnewplasmabiomarkersforalzheimersdisease AT miguelcalero tnapandp2x7rnewplasmabiomarkersforalzheimersdisease AT miguelmedina tnapandp2x7rnewplasmabiomarkersforalzheimersdisease AT migueldiazhernandez tnapandp2x7rnewplasmabiomarkersforalzheimersdisease |