Basic pathologies of neurodegenerative dementias and their relevance for state-of-the-art molecular imaging studies
Basic pathologies of neurodegenerative dementias and their relevance for state-of-the-art molecular imaging studies
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DOI：
10.1007/s00259-007-0697-6
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发表时间：
2008-03-01
影响因子：
9.1
通讯作者：
Drzezga, Alexander
中科院分区：
文献类型：
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作者：
Drzezga, Alexander
导言现代社会预期寿命的增长导致了痴呆症的迅速流行，特别是阿尔茨海默病(AD)。痴呆症成为最常见的与年龄相关的疾病之一，对相关患者及其亲属造成有害后果，并对社会经济系统产生令人担忧的影响。这些事实证明了加强科学努力来确定痴呆疾病的病理起源，提高诊断水平，并从治疗上干预疾病的进展。基本病理学近年来，在识别神经退行性疾病的潜在分子机制方面取得了显著进展。越来越多的证据表明，许多神经退行性痴呆的共同基础是蛋白质的产生增加、错误折叠和病理性聚集，如β-淀粉样蛋白、tau蛋白、α-突触核蛋白或最近描述的泛素化的TDP-43。在病理过程中的这种进步的洞察力与新治疗方法的发展是平行的。然而，不同病理在疾病发展中的确切作用或机制还不够清楚。在不同类型的临床定义的死后痴呆中，存在着相当大的病理学重叠，并且很难将死后组织病理学数据与生命中的疾病表现联系起来。分子成像技术可能在突破这一局限方面发挥有价值的作用。就成像研究而言，分子成像方法最近取得了令人印象深刻的进展，涌现了许多新的和改进的技术。这些令人兴奋的工具可能会在未来的病理机制评估、动物模型新诊断程序的临床前评估、临床试验患者的选择和治疗监测方面发挥关键作用。在这篇综述中，将对目前被认为与不同痴呆的发展密切相关的分子关键病理进行简要总结；还将讨论最先进的成像技术如何帮助现在和未来可视化这些过程。
Introduction Rising life-expectancy in the modern society has resulted in a rapidly growing prevalence of dementia, particularly of Alzheimer's disease (AD). Dementia turns into one of the most common age-related disorders with deleterious consequences for the concerned patients and their relatives, as well as worrying effects on the socio-economic systems. These facts justify strengthened scientific efforts to identify the pathologic origin of dementing disorders, to improve diagnosis, and to interfere therapeutically with the disease progression.Basic pathologies In the recent years, remarkable progress has been made concerning the identification of molecular mechanisms underlying the pathology of neurodegenerative disorders. Growing evidence indicates that a common basis of many neurodegenerative dementias can be found in increased production, misfolding and pathological aggregation of proteins, such as beta-amyloid, tau protein, a-synuclein, or the recently described ubiquitinated TDP-43. This progressive insight in pathological processes is paralleled by the development of new therapeutic approaches. However, the exact contribution or mechanism of different pathologies with regard to the development of disease is not yet sufficiently clear. Considerable overlap of pathologies has been documented in different types of clinically defined dementias post mortem, and it has been difficult to correlate post mortem histopathology data with disease-expression during life. Molecular imaging procedures may play a valuable role to circumvent this limitation.Relevance for imaging studies In general, methods of molecular imaging have recently experienced an impressive advance, with numerous new and improved technologies emerging. These exciting tools may play a key role in the future regarding the evaluation of pathomechanisms, preclinical evaluation of new diagnostic procedures in animal models, selection of patients for clinical trials, and therapy monitoring. In this overview, molecular key pathologies, which are currently regarded to be strongly associated with the development of different dementias, will be shortly summarized; it will also be discussed how state-of-the-art imaging technology can assist to visualize these processes now and in the future.