在阿尔茨海默病的所有病理阶段描绘人类海马体蛋白质组图谱。

Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease.

机构信息

Department of Pathology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.

出版信息

Alzheimers Dement. 2016 Jun;12(6):654-68. doi: 10.1016/j.jalz.2015.11.002. Epub 2016 Jan 6.

DOI:10.1016/j.jalz.2015.11.002

PMID:26772638

Abstract

INTRODUCTION

We performed a comprehensive quantitative proteomics study on human hippocampus tissue involving all Braak stages to assess changes in protein abundance over the various stages of Alzheimer's disease (AD).

METHODS

Hippocampal subareas CA1 and subiculum of 40 cases were isolated using laser capture microdissection and analyzed using mass spectrometry. Immunoblotting and immunohistochemistry were used for validation.

RESULTS

Over the Braak stages, an altered expression was found for 372 proteins including changes in levels of extracellular matrix components, and in calcium-dependent signaling proteins. Early changes were observed in levels of proteins related to cytoskeletal dynamics and synaptic components including an increase in RIMS1 and GRIK4. Several synaptic proteins, such as BSN, LIN7A, DLG2, -3, and -4, exhibit an early-up, late-down expression pattern.

DISCUSSION

This study provides new insight into AD-dependent changes in protein levels in the hippocampus during AD pathology, identifying potential novel therapeutic targets and biomarkers.

摘要

简介

我们对涉及阿尔茨海默病（AD）各阶段的人类海马组织进行了全面的定量蛋白质组学研究，以评估 AD 各阶段蛋白质丰度的变化。

方法

使用激光捕获显微切割分离 40 例海马区 CA1 和下托，并使用质谱进行分析。免疫印迹和免疫组织化学用于验证。

结果

在 Braak 阶段，发现 372 种蛋白质的表达发生改变，包括细胞外基质成分和钙依赖性信号蛋白水平的变化。在与细胞骨架动力学和突触成分相关的蛋白质水平上观察到早期变化，包括 RIMS1 和 GRIK4 的增加。几种突触蛋白，如 BSN、LIN7A、DLG2、-3 和 -4，表现出早期上调、晚期下调的表达模式。