Musunuri Sravani, Khoonsari Payam Emami, Mikus Maria, Wetterhall Magnus, Häggmark-Mänberg Anna, Lannfelt Lars, Erlandsson Anna, Bergquist Jonas, Ingelsson Martin, Shevchenko Ganna, Nilsson Peter, Kultima Kim
Analytical Chemistry, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University Academic Hospital, Uppsala, Sweden.
J Alzheimers Dis. 2016 Oct 18;54(4):1671-1686. doi: 10.3233/JAD-160271.
Alzheimer's disease (AD) is a chronic neurodegenerative disorder accounting for more than 50% of all dementia cases. AD neuropathology is characterized by the formation of extracellular plaques and intracellular neurofibrillary tangles consisting of aggregated amyloid-β and tau, respectively. The disease mechanism has only been partially elucidated and is believed to also involve many other proteins.
This study intended to perform a proteomic profiling of post mortem AD brains and compare it with control brains as well as brains from other neurological diseases to gain insight into the disease pathology.
Here we used label-free shotgun mass spectrometry to analyze temporal neocortex samples from AD, other neurological disorders, and non-demented controls, in order to identify additional proteins that are altered in AD. The mass spectrometry results were verified by antibody suspension bead arrays.
We found 50 proteins with altered levels between AD and control brains. The majority of these proteins were found at lower levels in AD. Pathway analyses revealed that several of the decreased proteins play a role in exocytic and endocytic pathways, whereas several of the increased proteins are related to extracellular vesicles. Using antibody-based analysis, we verified the mass spectrometry results for five representative proteins from this group of proteins (CD9, HSP72, PI42A, TALDO, and VAMP2) and GFAP, a marker for neuroinflammation.
Several proteins involved in exo-endocytic pathways and extracellular vesicle functions display altered levels in the AD brain. We hypothesize that such changes may result in disturbed cellular clearance and a perturbed cell-to-cell communication that may contribute to neuronal dysfunction and cell death in AD.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，占所有痴呆病例的50%以上。AD神经病理学的特征是分别由聚集的淀粉样β蛋白和tau蛋白形成细胞外斑块和细胞内神经原纤维缠结。该疾病机制仅得到部分阐明，并且据信还涉及许多其他蛋白质。
本研究旨在对AD患者死后的大脑进行蛋白质组分析，并将其与对照大脑以及其他神经系统疾病患者的大脑进行比较，以深入了解疾病病理学。
在这里，我们使用无标记鸟枪法质谱分析来自AD、其他神经系统疾病和非痴呆对照的颞叶新皮质样本，以鉴定在AD中发生改变的其他蛋白质。质谱结果通过抗体悬浮珠阵列进行验证。
我们发现AD大脑和对照大脑之间有50种蛋白质水平发生改变。这些蛋白质中的大多数在AD中含量较低。通路分析表明，几种减少的蛋白质在胞吐和内吞通路中起作用，而几种增加的蛋白质与细胞外囊泡有关。使用基于抗体的分析，我们验证了该组蛋白质中五种代表性蛋白质（CD9、HSP72、PI42A、TALDO和VAMP2）以及神经炎症标志物GFAP的质谱结果。
几种参与胞吐-内吞通路和细胞外囊泡功能的蛋白质在AD大脑中水平发生改变。我们假设这种变化可能导致细胞清除功能紊乱和细胞间通讯受到干扰，这可能导致AD中的神经元功能障碍和细胞死亡。
