Department of Clinical and Experimental Medicine, University of Pisa , Pisa, Italy.
Sorbonne University, GRC N° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de L'hôpital , Paris, France.
Expert Rev Proteomics. 2020 Jul-Aug;17(7-8):543-559. doi: 10.1080/14789450.2020.1831388. Epub 2020 Oct 18.
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).
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.
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.
有证据表明，在神经退行性疾病（NDD）中，尤其是在阿尔茨海默病（AD）中，突触密度与认知表现密切相关，这为寻找可靠的流体生物标志物来跟踪突触功能障碍提供了依据。
神经颗粒蛋白（Ng）是一种主要表达在参与记忆网络的神经元中的突触后蛋白。目前，脑脊液中的 Ng 是最有前途的突触生物标志物。多项研究表明，AD 痴呆患者（伴有海马表型）和进展为 AD 的轻度认知障碍（MCI）患者的脑脊液 Ng 升高。在广泛而大量的突触解体的克雅氏病（Creutzfeldt Jacob Disease）中，Ng 浓度也会增加。Ng 不能区分帕金森病和非典型帕金森病，也不会在亨廷顿病中改变。脑脊液突触体相关蛋白 25（SNAP-25）和突触结合蛋白-1（SYT-1）是新兴的候选标志物。
脑脊液 Ng 被揭示为 NDD 的一种诊断和预后生物标志物。Ng 的增加似乎对典型的 AD 表型非常特异，可能与普遍的海马受累有关。突触生物标志物在 AD 和其他 NDD 中可能具有不同的用途，包括预后、诊断和跟踪突触损伤——这是 NDD 的一个关键病理生理机制——因此，它们是针对 NDD 的精准医疗方法的可靠工具。
