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阿尔茨海默病患者血浆外泌体神经颗粒蛋白与脑结构的相关性:一项方案研究。

Association between plasma exosome neurogranin and brain structure in patients with Alzheimer's disease: a protocol study.

机构信息

Department of Neurology, HongQi Hospital, Mudanjiang Medical University, Mudanjiang, China.

Heilongjiang Key Laboratory of Ischemic Stroke Prevention and Treatment, Mudanjiang Medical University, Mudanjiang, China.

出版信息

BMJ Open. 2020 Aug 16;10(8):e036990. doi: 10.1136/bmjopen-2020-036990.

Abstract

INTRODUCTION

Neurogranin is known to be significantly elevated in patients with Alzheimer's disease (AD) and may be an effective clinical predictor of cognitive decline and neurodegeneration. Amnestic mild cognitive impairment (aMCI) is an intermediate disease state between normal cognitive ageing and dementia, the latter of which can easily revert to AD. There remains significant uncertainty regarding the conversion of aMCI to AD, and therefore, elucidating such progression is paramount to the field of cognitive neuroscience. In this protocol study, we therefore aim to investigate the changes in plasma neurogranin in the early stage of AD and the mechanism thereof regarding the cognitive progression towards AD.

METHODS AND ANALYSIS

In this study, patients with aMCI and AD patients (n=70 each) will be recruited at the memory clinic of the Department of Neurology of Hongqi Hospital affiliated with the Mudanjiang Medical University of China. Healthy older controls (n=70) will also be recruited from the community. All subjects will undergo neuroimaging and neuropsychological evaluations in addition to blood collection at the first year and the third year. We hope to identify a new biomarker of cognitive decline associated with AD and characterise its behaviour throughout the progression of aMCI to AD. This work will reveal novel targets for the therapeutic prevention, diagnosis and treatment of AD. The primary outcome measures will be (1) neuropsychological evaluation, including Mini-Mental State Examination, Montreal Cognitive Assessment, Clinical Dementia Rating scale, Shape Trail Test-A&B, Auditory Verbal Learning Test-HuaShan version; (2) microstructural alterations and hippocampal features from MRI scans; and (3) neurogranin levels in the neuronal-derived exosomes from peripheral blood samples.

ETHICS AND DISSEMINATION

The ethics committee of the Hongqi Hospital affiliated with the Mudanjiang Medical University of China has approved this study protocol. The results will be published in peer-reviewed journals and presented at national or international scientific conferences.

TRIAL REGISTRATION NUMBER

ChiCTR2000029055.

摘要

简介

神经颗粒蛋白(Neurogranin)已知在阿尔茨海默病(AD)患者中显著升高,可能是认知能力下降和神经退行性变的有效临床预测指标。遗忘型轻度认知障碍(aMCI)是正常认知老化和痴呆之间的中间疾病状态,后者很容易逆转为 AD。关于 aMCI 向 AD 的转化仍存在很大的不确定性,因此,阐明这种进展对于认知神经科学领域至关重要。在本方案研究中,我们旨在研究 AD 早期血浆神经颗粒蛋白的变化及其向 AD 认知进展的机制。

方法与分析

本研究将在中国牡丹江市红旗医院神经内科记忆诊所招募 70 名 aMCI 患者和 AD 患者,同时还将从社区招募 70 名健康老年人对照者。所有受试者将在第一年和第三年进行神经影像学和神经心理学评估以及血液采集。我们希望确定与 AD 相关的认知下降的新生物标志物,并描述其在从 aMCI 到 AD 的进展过程中的行为。这项工作将为 AD 的治疗预防、诊断和治疗揭示新的靶点。主要的观察指标将包括(1)神经心理学评估,包括简易精神状态检查、蒙特利尔认知评估、临床痴呆评定量表、形状追踪测试 A&B、听觉词语学习测试-华山版;(2)来自 MRI 扫描的微结构改变和海马特征;(3)外周血神经元衍生外泌体中的神经颗粒蛋白水平。

伦理和传播

中国牡丹江市红旗医院的伦理委员会已批准了本研究方案。研究结果将发表在同行评议的期刊上,并在国内或国际科学会议上展示。

注册号

ChiCTR2000029055。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47a4/7430441/e1ffd691358b/bmjopen-2020-036990f01.jpg

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