ABSTRACT

Introduction

The quest for reliable fluid biomarkers tracking synaptic disruption is supported by the evidence of a tight association between synaptic density and cognitive performance in neurodegenerative diseases (NDD), especially Alzheimer’s disease (AD).

Areas covered

Neurogranin (Ng) is a post-synaptic protein largely expressed in neurons involved in the memory networks. Currently, Ng measured in CSF is the most promising synaptic biomarker. Several studies show Ng elevated in AD dementia with a hippocampal phenotype as well as in MCI individuals who progress to AD. Ng concentrations are also increased in Creutzfeldt Jacob Disease where widespread and massive synaptic disintegration takes place. Ng does not discriminate Parkinson’s disease from atypical parkinsonisms, nor is it altered in Huntington disease. CSF synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin‐1 (SYT-1) are emerging candidates.

Expert opinion

CSF Ng revealed a role as a diagnostic and prognostic biomarker in NDD. Ng increase seems to be very specific for typical AD phenotype, probably for a prevalent hippocampal involvement. Synaptic biomarkers may serve different context-of-use in AD and other NDD including prognosis, diagnosis, and tracking synaptic damage – a critical pathophysiological mechanism in NDD – thus representing reliable tools for a precision medicine-oriented approach to NDD.

中文翻译：

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突触生物标志物在神经退行性疾病谱中的作用

摘要

介绍

突触密度与神经退行性疾病（NDD），尤其是阿尔茨海默病（AD）的认知表现之间存在紧密关联的证据支持了对追踪突触破坏的可靠液体生物标志物的探索。

覆盖区域

神经颗粒蛋白 (Ng) 是一种突触后蛋白，主要在参与记忆网络的神经元中表达。目前，在 CSF 中测量的 Ng 是最有希望的突触生物标志物。几项研究表明，在具有海马表型的 AD 痴呆以及进展为 AD 的 MCI 个体中，Ng 升高。在发生广泛和大规模突触解体的克罗伊茨费尔特雅各布病中，Ng 浓度也增加。Ng 没有将帕金森病与非典型帕金森病区分开来，在亨廷顿病中也没有改变。CSF 突触体相关蛋白 25 (SNAP-25) 和突触结合蛋白-1 (SYT-1) 是新兴的候选者。

专家意见

CSF Ng 揭示了作为 NDD 诊断和预后生物标志物的作用。Ng 增加似乎对典型的 AD 表型非常具有特异性，可能是普遍存在的海马受累。突触生物标志物可以在 AD 和其他 NDD 中提供不同的使用环境，包括预后、诊断和跟踪突触损伤——NDD 的一个关键病理生理机制——因此代表了以精准医学为导向的 NDD 方法的可靠工具。