Bistaffa Edoardo, Tagliavini Fabrizio, Matteini Paolo, Moda Fabio
Fondazione IRCCS Istituto Neurologico Carlo Besta, Division of Neurology 5 and Neuropathology, 20133 Milan, Italy.
Fondazione IRCCS Istituto Neurologico Carlo Besta, Scientific Directorate, 20133 Milan, Italy.
Brain Sci. 2020 Nov 3;10(11):815. doi: 10.3390/brainsci10110815.
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. The distinctive neuropathological feature of AD is the intracerebral accumulation of two abnormally folded proteins: β-amyloid (Aβ) in the form of extracellular plaques, and tau in the form of intracellular neurofibrillary tangles. These proteins are considered disease-specific biomarkers, and the definite diagnosis of AD relies on their post-mortem identification in the brain. The clinical diagnosis of AD is challenging, especially in the early stages. The disease is highly heterogeneous in terms of clinical presentation and neuropathological features. This phenotypic variability seems to be partially due to the presence of distinct Aβ conformers, referred to as strains. With the development of an innovative technique named Real-Time Quaking-Induced Conversion (RT-QuIC), traces of Aβ strains were found in the cerebrospinal fluid of AD patients. Emerging evidence suggests that different conformers may transmit their strain signature to the RT-QuIC reaction products. In this review, we describe the current challenges for the clinical diagnosis of AD and describe how the RT-QuIC products could be analyzed by a surface-enhanced Raman spectroscopy (SERS)-based systems to reveal the presence of strain signatures, eventually leading to early diagnosis of AD with the recognition of individual disease phenotype.
阿尔茨海默病（AD）是全球最常见的神经退行性疾病。AD的独特神经病理学特征是两种异常折叠蛋白在脑内的积累：细胞外斑块形式的β-淀粉样蛋白（Aβ）和细胞内神经原纤维缠结形式的tau蛋白。这些蛋白被认为是疾病特异性生物标志物，AD的明确诊断依赖于在大脑中进行尸检鉴定。AD的临床诊断具有挑战性，尤其是在早期阶段。该疾病在临床表现和神经病理学特征方面具有高度异质性。这种表型变异性似乎部分归因于不同的Aβ构象异构体（称为毒株）的存在。随着一种名为实时震颤诱导转化（RT-QuIC）的创新技术的发展，在AD患者的脑脊液中发现了微量的Aβ毒株。新出现的证据表明，不同的构象异构体可能将其毒株特征传递给RT-QuIC反应产物。在这篇综述中，我们描述了AD临床诊断当前面临的挑战，并描述了如何通过基于表面增强拉曼光谱（SERS）的系统分析RT-QuIC产物，以揭示毒株特征的存在，最终通过识别个体疾病表型实现AD的早期诊断。
