Laboratory of Amyloid Biology, St. Petersburg State University, St. Petersburg, Russia.
I.P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
Prion. 2021 Dec;15(1):56-69. doi: 10.1080/19336896.2021.1917289.
Alzheimer's disease (AD) is the most common form of dementia that usually occurs among older people. AD results from neuronal degeneration that leads to the cognitive impairment and death. AD is incurable, typically develops over the course of many years and is accompanied by a loss of functional autonomy, making a patient completely dependent on family members and/or healthcare workers. Critical features of AD are pathological polymerization of Aβ peptide and microtubule-associated protein tau, accompanied by alterations of their conformations and resulting in accumulation of cross-β fibrils (amyloids) in human brains. AD apparently progresses asymptomatically for years or even decades before the appearance of symptoms. Therefore, development of the early AD diagnosis at a pre-symptomatic stage is essential for potential therapies. This review is focused on current and potential molecular tools (including non-invasive methods) that are based on detection of amyloidogenic proteins and can be applicable to early diagnosis of AD.: Aβ - amyloid-β peptide; AβO - amyloid-β oligomers; AD - Alzheimer's disease; ADRDA - Alzheimer's Disease and Related Disorders Association; APH1 - anterior pharynx defective 1; APP - amyloid precursor protein; BACE1 - β-site APP-cleaving enzyme 1; BBB - brain blood barrier; CJD - Creutzfeldt-Jakob disease; CRM - certified reference material; CSF - cerebrospinal fluid; ELISA - enzyme-linked immunosorbent assay; FGD - F-fluorodesoxyglucose (2-deoxy-2-[F]fluoro-D-glucose); IP-MS - immunoprecipitation-mass spectrometry assay; MCI - mild cognitive impairment; MDS - multimer detection system; MRI - magnetic resonance imaging; NIA-AA - National Institute on Ageing and Alzheimer's Association; NINCDS - National Institute of Neurological and Communicative Disorders and Stroke; PEN2 - presenilin enhancer 2; PET - positron emission tomography; PiB - Pittsburgh Compound B; PiB-SUVR - PIB standardized uptake value ratio; PMCA - Protein Misfolding Cycling Amplification; PrP - Prion Protein; P-tau - hyperphosphorylated tau protein; RMP - reference measurement procedure; RT-QuIC - real-time quaking-induced conversion; SiMoA - single-molecule array; ThT - thioflavin T; TSEs - Transmissible Spongiform Encephslopathies; T-tau - total tau protein.
阿尔茨海默病（AD）是最常见的痴呆症形式，通常发生在老年人中。AD 是由神经元变性引起的，导致认知障碍和死亡。AD 是无法治愈的，通常在多年的过程中发展，并伴随着功能自主性的丧失，使患者完全依赖于家庭成员和/或医护人员。AD 的关键特征是 Aβ肽和微管相关蛋白 tau 的病理性聚合，伴随着它们构象的改变，导致人类大脑中交叉β纤维（淀粉样蛋白）的积累。AD 在出现症状前显然会无症状地进展数年甚至数十年。因此，在出现症状前的无症状阶段开发早期 AD 诊断对于潜在的治疗至关重要。本综述重点介绍了当前和潜在的分子工具（包括非侵入性方法），这些工具基于对淀粉样蛋白形成蛋白的检测，可应用于 AD 的早期诊断：Aβ-淀粉样-β肽；AβO-淀粉样-β寡聚物；AD-阿尔茨海默病；ADRDA-阿尔茨海默病及相关疾病协会；APH1-前咽缺陷 1；APP-淀粉样前体蛋白；BACE1-β-位点 APP 切割酶 1；BBB-血脑屏障；CJD-克雅氏病；CRM-认证参考物质；CSF-脑脊液；ELISA-酶联免疫吸附测定；FGD-F-氟脱氧葡萄糖（2-脱氧-2-[F]氟-D-葡萄糖）；IP-MS-免疫沉淀-质谱分析；MCI-轻度认知障碍；MDS-多聚体检测系统；MRI-磁共振成像；NIA-AA-国家老龄化研究所和阿尔茨海默病协会；NINCDS-国家神经疾病和中风研究所；PEN2-早老素增强子 2；PET-正电子发射断层扫描；PiB-匹兹堡化合物 B；PiB-SUVR-PiB 标准化摄取值比；PMCA-蛋白质错误折叠循环扩增；PrP-Prion 蛋白；P-tau-过度磷酸化 tau 蛋白；RMP-参考测量程序；RT-QuIC-实时震颤诱导转化；SiMoA-单分子阵列；ThT-硫黄素 T；TSEs-传染性海绵状脑病；T-tau-总 tau 蛋白。
