Mass Spectrometry Imaging in Alzheimer's Disease
Mass Spectrometry Imaging in Alzheimer's Disease
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DOI：
10.1089/brain.2022.0057
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发表时间：
2023-04-24
影响因子：
3.4
通讯作者：
Hanrieder，Jorg
中科院分区：
文献类型：
--
作者：
Ikegawa，Masaya;Kakuda，Nobuto;Hanrieder，Jorg
前言：淀粉样β蛋白(Aβ)病理是阿尔茨海默病(AD)的组织病理学特征。虽然人类大脑中淀粉样斑块的形成被认为是启动AD发病的关键因素，但导致Aβ斑块形成的上游事件及其在脑内的代谢仍未完全清楚。方法：已成功地将基质辅助激光解吸电离质谱仪应用于AD小鼠模型和人类样本的脑组织病理研究。结果：MALDI-MSI显示AD脑内有较短的多肽沉积，Aβ1-36和Aβ1-39的分布与Aβ1-40的分布非常相似，Aβ1-42和Aβ1-43的沉积具有明显的老年性斑块分布在脑实质中。此外，本文还对MALDI-MSI在斑块病理谷氨酸脂体组学中的应用进行了综述，认为神经元脂质生物化学中的异常与AD的发病机制有关。不同的A-β亚型，包括在AD和CAA脑组织中的各种C-端和N-端截断将被可视化。尽管血管和斑块Aβ沉积之间存在密切关系，但目前的策略将在Aβ代谢水平上定义神经退行性变和脑血管过程之间的串扰。
Introduction:Amyloid-beta (Aβ) pathology is the precipitating histopathological characteristic of Alzheimer's disease (AD). Although the formation of amyloid plaques in human brains is suggested to be a key factor in initiating AD pathogenesis, it is still not fully understood the upstream events that lead to Aβ plaque formation and its metabolism inside the brains.Methods:Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) has been successfully introduced to study AD pathology in brain tissue both in AD mouse models and human samples. By using MALDI-MSI, a highly selective deposition of Aβ peptides in AD brains with a variety of cerebral amyloid angiopathy (CAA) involvement was observed.Results:MALDI-MSI visualized depositions of shorter peptides in AD brains; Aβ1–36 to Aβ1–39 were quite similarly distributed with Aβ1–40 as a vascular pattern, and deposition of Aβ1–42 and Aβ1–43 was visualized with a distinct senile plaque pattern distributed in parenchyma. Moreover, how MALDI-MSI coveredin situlipidomics of plaque pathology has been reviewed, which is of interest as aberrations in neuronal lipid biochemistry have been implicated in AD pathogenesis.Discussion:In this study, we introduce the methodological concepts and challenges of MALDI-MSI for the studies of AD pathogenesis. Diverse Aβ isoforms including various C- and N-terminal truncations in AD and CAA brain tissues will be visualized. Despite the close relationship between vascular and plaque Aβ deposition, the current strategy will define cross talk between neurodegenerative and cerebrovascular processes at the level of Aβ metabolism.