Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, VIC, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Alzheimers Dement. 2014 Jun;10(3 Suppl):S254-64. doi: 10.1016/j.jalz.2014.04.013.
The military conflicts of the last decade have highlighted the growing problem of traumatic brain injury in combatants returning from the battlefield. The considerable evidence pointing at the accumulation of tau aggregates and its recognition as a risk factor in neurodegenerative conditions such as Alzheimer's disease have led to a major effort to develop selective tau ligands that would allow research into the physiopathologic underpinnings of traumatic brain injury and chronic traumatic encephalopathy in military personnel and the civilian population. These tracers will allow new insights into tau pathology in the human brain, facilitating research into causes, diagnosis, and treatment of traumatic encephalopathy and major neurodegenerative dementias, such as Alzheimer's disease and some variants of frontotemporal lobar degeneration, in which tau plays a role. The field of selective tau imaging has to overcome several obstacles, some of them associated with the idiosyncrasies of tau aggregation and others related to radiotracer design. A worldwide effort has focused on the development of imaging agents that will allow selective tau imaging in vivo. Recent progress in the development of these tracers is enabling the noninvasive assessment of the extent of tau pathology in the brain, eventually allowing the quantification of changes in tau pathology over time and its relation to cognitive performance, brain volumetrics, and other biomarkers, as well as assessment of efficacy and patient recruitment for antitau therapeutic trials.
过去十年的军事冲突凸显了战场上归来的战斗人员创伤性脑损伤问题日益严重。大量证据表明，tau 聚集物的积累及其被认为是阿尔茨海默病等神经退行性疾病的一个风险因素，这促使人们大力开发选择性 tau 配体，以便能够研究军事人员和普通人群中创伤性脑损伤和慢性创伤性脑病的病理生理基础。这些示踪剂将使人们对人类大脑中的 tau 病理学有新的认识，有助于研究创伤性脑病和主要神经退行性痴呆症（如阿尔茨海默病和某些额颞叶变性变体）的病因、诊断和治疗，tau 在其中发挥作用。选择性 tau 成像领域必须克服几个障碍，其中一些与 tau 聚集的特殊性有关，另一些与放射性示踪剂设计有关。全世界都在努力开发能够在体内选择性地进行 tau 成像的成像剂。这些示踪剂的最新进展使人们能够对大脑中 tau 病理学的程度进行无创评估，最终可以随着时间的推移定量评估 tau 病理学的变化及其与认知表现、脑容积和其他生物标志物的关系，以及评估抗 tau 治疗试验的疗效和患者招募情况。
