Neurogranin and Neuronal Pentraxin Receptor as Synaptic Dysfunction Biomarkers in Alzheimer's Disease.

Maciej Dulewicz,Agnieszka Kulczyńska-Przybik,Agnieszka Słowik,Barbara Mroczko,Renata Borawska

doi:10.3390/jcm10194575

Maciej Dulewicz, Agnieszka Kulczyńska-Przybik + Show 3 more

Open Access

https://doi.org/10.3390/jcm10194575

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Abstract

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the early stage of the disease. To our best knowledge, this is the first study that analyzes the CSF concentrations of two synaptic proteins together, such as neurogranin (Ng) and neuronal pentraxins receptor (NPTXR) in relation to neurochemical dementia biomarkers in Alzheimer’s disease. Methods: Ng, NPTXR and classical AD biomarkers concentrations were measured in the CSF of patients with AD and non-demented controls (CTRL) using an enzyme-linked immunosorbent assay (ELISA) and Luminex xMAP technology. Results: The CSF level of Ng was significantly higher, whereas the NPTXR was significantly lower in the AD patients than in cognitively healthy controls. As a first, we calculated the NPTXR/Ng ratio as an indicator of synaptic disturbance. The patients with AD presented a significantly decreased NPTXR/Ng ratio. The correlation was observed between both proteins in the AD and the whole study group. Furthermore, the relationship between the Ng level and pTau181 was found in the AD group of patients. Conclusions: The Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD.

Highlights

Alzheimer’s disease (AD) is the most common neurodegenerative disease dependent on many neuropathological processes [1,2]
We examined the concentrations of the following two proteins associated with synaptic plasticity and glutamatergic receptors: neurogranin (Ng) and neuronal pentraxin receptor (NPTXR)
Based on the MMSE score, biochemical analyses and clinical picture, we chose patients with not very advanced AD because we aimed to check if the concentrations of selected synaptic proteins may reflect the early synaptic pathology and there is a relationship with amyloid and tau biomarkers in the early phase of full-blown disease

Summary

Introduction

Alzheimer’s disease (AD) is the most common neurodegenerative disease dependent on many neuropathological processes [1,2]. One of the earliest symptoms of Alzheimer’s disease is cognitive impairment, including memory disturbances [3,4]. Memory and learning processes are associated with neuronal communications and hippocampal functions maintained by synapses [3,5]. Impairment of cognitive deficits in AD is associated with neuronal transmission between synapses and neurodegenerative changes [3,6]. The research focused on finding functional pre- and post-synaptic proteins that can contribute to a better understanding of neurobiological mechanisms of AD and improve early diagnosis [3,7]. One of the most important processes involved in memory is long-term potentiation (LTP)

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