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Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD) and other neurodegenerative diseases. This study aimed to assess the relationships between biological processes of the synaptic pathology underlying AD, mole...

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Autores principales: Dulewicz, Maciej, Kulczyńska-Przybik, Agnieszka, Borawska, Renata, Słowik, Agnieszka, Mroczko, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502777/
https://www.ncbi.nlm.nih.gov/pubmed/36142780
http://dx.doi.org/10.3390/ijms231810867
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author Dulewicz, Maciej
Kulczyńska-Przybik, Agnieszka
Borawska, Renata
Słowik, Agnieszka
Mroczko, Barbara
author_facet Dulewicz, Maciej
Kulczyńska-Przybik, Agnieszka
Borawska, Renata
Słowik, Agnieszka
Mroczko, Barbara
author_sort Dulewicz, Maciej
collection PubMed
description Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD) and other neurodegenerative diseases. This study aimed to assess the relationships between biological processes of the synaptic pathology underlying AD, molecular functions, and dynamics of the change concentrations of selected proteins reflecting synaptic and axonal pathology in dementia stages. Neurogranin (Ng), neuronal pentraxin receptor (NPTXR), and Visinin-like protein 1 (VILIP1) concentrations were measured in the cerebrospinal fluid (CSF) of MCI, AD, and non-demented controls (CTRL) using quantitative immunological methods. Gene ontology (GO) enrichment analysis was used for the functional analysis of tested proteins. The CSF Aβ42/Ng ratio was significantly different between all the compared groups. The CSF NPTXR/Ng ratio was significantly different between MCI compared to CTRL and AD compared to CTRL. The GO enrichment analysis revealed that two terms (the Biological Process (BP) and Cellular Component (CC) levels) are significantly enriched for NPTXR and Ng but not for VILIP1. Both Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers for the early diagnosis of the disease. Moreover, both proteins are biochemically associated with classical biomarkers and VILIP-1. Mapping shared molecular and biological functions for the tested proteins by GO enrichment analysis may be beneficial in screening and setting new research targets.
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spelling pubmed-95027772022-09-24 Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis Dulewicz, Maciej Kulczyńska-Przybik, Agnieszka Borawska, Renata Słowik, Agnieszka Mroczko, Barbara Int J Mol Sci Article Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD) and other neurodegenerative diseases. This study aimed to assess the relationships between biological processes of the synaptic pathology underlying AD, molecular functions, and dynamics of the change concentrations of selected proteins reflecting synaptic and axonal pathology in dementia stages. Neurogranin (Ng), neuronal pentraxin receptor (NPTXR), and Visinin-like protein 1 (VILIP1) concentrations were measured in the cerebrospinal fluid (CSF) of MCI, AD, and non-demented controls (CTRL) using quantitative immunological methods. Gene ontology (GO) enrichment analysis was used for the functional analysis of tested proteins. The CSF Aβ42/Ng ratio was significantly different between all the compared groups. The CSF NPTXR/Ng ratio was significantly different between MCI compared to CTRL and AD compared to CTRL. The GO enrichment analysis revealed that two terms (the Biological Process (BP) and Cellular Component (CC) levels) are significantly enriched for NPTXR and Ng but not for VILIP1. Both Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers for the early diagnosis of the disease. Moreover, both proteins are biochemically associated with classical biomarkers and VILIP-1. Mapping shared molecular and biological functions for the tested proteins by GO enrichment analysis may be beneficial in screening and setting new research targets. MDPI 2022-09-17 /pmc/articles/PMC9502777/ /pubmed/36142780 http://dx.doi.org/10.3390/ijms231810867 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dulewicz, Maciej
Kulczyńska-Przybik, Agnieszka
Borawska, Renata
Słowik, Agnieszka
Mroczko, Barbara
Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis
title Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis
title_full Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis
title_fullStr Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis
title_full_unstemmed Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis
title_short Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis
title_sort evaluation of synaptic and axonal dysfunction biomarkers in alzheimer’s disease and mild cognitive impairment based on csf and bioinformatic analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502777/
https://www.ncbi.nlm.nih.gov/pubmed/36142780
http://dx.doi.org/10.3390/ijms231810867
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