Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer's Disease.

Luisa Agnello,Vincenzo La Bella,Giulia Bivona,Matteo Vidali,Marcello Ciaccio,Bruna Lo Sasso,Anna Maria Ciaccio,Caterina Maria Gambino,Rosaria Vincenza Giglio,Concetta Scazzone,Tommaso Piccoli

doi:10.3390/diagnostics11122339

Abstract

(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer’s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological diseases (n = 70) and controls (33). We measured CSF neurogranin levels by a commercial ELISA kit. CSF RI of neurogranin was calculated by a robust method; (3) Results: AD patients showed increased levels of neurogranin. We also found that neurogranin was significantly correlated with T-tau, P-tau and mini mental state examination in AD patients. The lower and upper reference limits of the RI were 2.9 (90%CI 0.1–10.8) and 679 (90%CI 595–779), respectively; (4) Conclusion: This is the first study establishing the RI of CSF neurogranin.

Highlights

Neurogranin is a calmodulin-binding protein discovered in 1990, but only in recent years it gained attention as a potential biomarker of neurodegeneration [1]
In the last few decades, research has focused on the possible role of neurogranin as a biomarker for synaptic dysfunction in neurodegenerative diseases, such as Alzheimer’s disease (AD) [7,8]
Neurogranin levels have been found to be markedly reduced in the frontal cortex and hippocampus, whereas they are found to be increased in the cerebrospinal fluid (CSF) of AD patients, indicating loss of post-synaptic elements in the extracellular space [10,11,12,13]

Summary

Introduction

Neurogranin is a calmodulin-binding protein discovered in 1990, but only in recent years it gained attention as a potential biomarker of neurodegeneration [1]. The term “neurogranin” refers to its expression in granule-like structures within excitatory neurons of the hippocampus and cerebral cortex [2]. It is a post-synaptic protein with a pivotal role in regulating synaptic plasticity and function [3,4]. In the last few decades, research has focused on the possible role of neurogranin as a biomarker for synaptic dysfunction in neurodegenerative diseases, such as Alzheimer’s disease (AD) [7,8]. Neurogranin levels have been found to be markedly reduced in the frontal cortex and hippocampus, whereas they are found to be increased in the CSF of AD patients, indicating loss of post-synaptic elements in the extracellular space [10,11,12,13]

Objectives

Methods

Results