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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Bibliographic Details
Published in:International journal of molecular sciences 2022-09, Vol.23 (18), p.10867
Main Authors: Dulewicz, Maciej, Kulczyńska-Przybik, Agnieszka, Borawska, Renata, Słowik, Agnieszka, Mroczko, Barbara
Format: Article
Language:English
Subjects:
Accuracy
Alzheimer's disease
Bioinformatics
Biological activity
Biomarkers
Cerebrospinal fluid
CSF synaptic biomarkers
Dementia
Dementia disorders
Enrichment
Functional analysis
Genes
Immunology
Neurocalcin
Neurodegeneration
Neurogranin
neuronal pentraxin receptor
Pathogenesis
Pathology
Pentraxins
Peptide mapping
Proteins
Ratios
Visinin-like protein 1
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231810867