脑脊液中突触蛋白神经颗粒蛋白水平与前驱期阿尔茨海默病认知能力下降相关。

Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer's disease.

机构信息

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

出版信息

Alzheimers Dement. 2015 Oct;11(10):1180-90. doi: 10.1016/j.jalz.2014.10.009. Epub 2014 Dec 19.

DOI:10.1016/j.jalz.2014.10.009

PMID:25533203

Abstract

INTRODUCTION

Synaptic dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and directly related to cognitive impairment. Consequently, synaptic biomarkers may be valuable tools for both early diagnosis and disease stage. Neurogranin (Ng) is a postsynaptic protein involved in memory consolidation.

METHODS

We developed three monoclonal anti-Ng antibodies. Mass spectrometry and a novel enzyme-linked immunosorbent assay were used to analyze cerebrospinal fluid (CSF) Ng in three independent clinical cohorts including patients with AD dementia (n = 100 in total), mild cognitive impairment patients (MCI), (n = 40) and controls (n = 80 in total).

RESULTS

We show in three independent clinical cohorts a marked increase in CSF Ng levels in AD dementia (P < .001 in all studies). In addition, high CSF Ng levels at the MCI stage predicted progression to dementia due to AD with a hazard ratio of 12.8 (95% confidence interval 1.6-103.0, P = .02). In amyloid-positive MCI patients, high CSF Ng correlated with a more rapid change in cognition during clinical follow-up (P = .03).

DISCUSSION

These results suggest that CSF Ng is a novel AD biomarker that may be used to monitor synaptic degeneration, and correlates with the rate of cognitive decline in prodromal AD.

摘要

简介

突触功能障碍是阿尔茨海默病（AD）发病机制中的早期事件，与认知障碍直接相关。因此，突触生物标志物可能是早期诊断和疾病分期的有价值的工具。神经颗粒蛋白（Ng）是一种参与记忆巩固的突触后蛋白。

方法

我们开发了三种单克隆抗 Ng 抗体。质谱和一种新的酶联免疫吸附试验用于分析三个独立临床队列的脑脊液（CSF）Ng，包括 AD 痴呆患者（共 100 例）、轻度认知障碍患者（MCI）（共 40 例）和对照组（共 80 例）。

结果

我们在三个独立的临床队列中显示，AD 痴呆患者的 CSF Ng 水平显著升高（所有研究中均<.001）。此外，MCI 阶段高 CSF Ng 水平预示着 AD 导致的痴呆进展，风险比为 12.8（95%置信区间 1.6-103.0，P =.02）。在淀粉样蛋白阳性的 MCI 患者中，高 CSF Ng 与临床随访期间认知变化的速度呈正相关（P =.03）。