Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, USA.
Curr Alzheimer Res. 2011 May;8(3):273-94. doi: 10.2174/156720511795563700.
The first reports of disorders that in terms of cognitive and behavioral symptoms resemble frontotemporal dementia (FTD) and in terms of motor symptoms resemble amyotrophic lateral sclerosis (ALS) bring us back to the second half of the 1800s. Over the last 150 years, and especially in the last two decades, there has been growing evidence that FTD signs can be seen in patients primarily diagnosed with ALS, implying clinical overlap among these two disorders. In the last decade pathological investigations and genetic screening have contributed tremendously in elucidating the pathology and genetic variability associated with FTD and ALS. To the most important recentdiscoveries belong TAR DNA binding protein [TARDBP or TDP-43] and the fused in sarcoma gene [FUS] and their implication in these disorders.FTD and ALS are the focus of this review which aims to 1. summarize clinical features by describing the diagnostic criteria and specific symptomatology, 2. describe the morphological aspects and related pathology, 3. describe the genetic factors associated with the diseases and 4. summarize the current status of clinical trials and treatment options. A better understanding of the clinical, pathological and genetic features characterizing FTD and ALS will shed light into overlaps among these two disorders and the underpinning mechanisms that contribute to the onset and development. Nevertheless, advancements in the knowledge of the biology of these two disorders will help developing novel and, hopefully, more effective diagnostic and treatment options.
首例以认知和行为症状类似于额颞叶痴呆（FTD），以运动症状类似于肌萎缩侧索硬化症（ALS）为特征的疾病报告可追溯到 19 世纪下半叶。在过去的 150 年里，特别是在过去的二十年中，越来越多的证据表明，FTD 症状可在主要诊断为 ALS 的患者中看到，这意味着这两种疾病之间存在临床重叠。在过去的十年中，病理研究和基因筛查极大地阐明了与 FTD 和 ALS 相关的病理学和遗传变异性。最近最重要的发现包括 TAR DNA 结合蛋白 [TARDBP 或 TDP-43] 和肉瘤融合基因 [FUS]，以及它们在这些疾病中的作用。FTD 和 ALS 是本综述的重点，旨在：1. 通过描述诊断标准和特定症状总结临床特征；2. 描述形态学方面和相关病理学；3. 描述与疾病相关的遗传因素；4. 总结目前的临床试验和治疗选择。更好地了解 FTD 和 ALS 的临床、病理和遗传特征将揭示这两种疾病之间的重叠以及导致其发病和发展的潜在机制。然而，对这两种疾病生物学的深入了解将有助于开发新的、有希望更有效的诊断和治疗选择。
