New Clinical Approaches to Creutzfeldt-Jakob Disease

描述(申请人提供)：克雅氏病(CJD)是一种进展迅速、普遍致命和可传播的神经退行性疾病，给患者及其家人带来可怕的负担。奎纳克林可能是治疗CJD的一种潜在疗法，这一最近的发现可能对患者产生巨大的影响。不幸的是，患者通常是在疾病的晚期被诊断出来的--在这段时间里，可用的治疗可能无效。这种延迟诊断的部分原因是，目前散发性CJD(SCJD)的临床标准是基于一系列症状，这些症状通常只出现在患者病程的后期。 最近，神经成像显示出提高sCJD诊断的潜力。此外，脑脊液中蛋白14-3-3水平的升高被认为是sCJD的敏感和特异的生物标志物，最近被添加到sCJD的诊断标准中。然而，还没有系统的研究来确定这两种类型的生物标记物在病理证实的sCJD和非Prion快速进行性痴呆中的敏感性和特异性。 这项建议的研究目标集中在通过对临床和影像表现的系统分析来确定早期诊断CJD的更好方法。这项研究的具体目标如下： 1.目的：确定弥散加权成像(DWI)序列异常对散发性CJD的敏感性和特异性，以及 2.探讨脑脊液14-3-3蛋白作为散发性CJD标志物的敏感性和特异性。 这项研究将为SCJD的早期特征提供新的信息，从而有助于诊断。此外，这项建议将结合教学、指导和临床研究经验，以格施温德博士在行为神经学和神经科学方面的培训为基础，从而帮助他设计和实施未来人类普恩病毒病和其他痴呆的临床治疗研究。

DESCRIPTION (provided by applicant): Creutzfeldt-Jakob disease (CJD)is a rapidly progressive, universally fatal, and transmissible neurodegenerative disease that imposes a terrible burden on patients and their families. The recent discovery that quinacrine may be a potential therapy for CJD could have enormous implications for patients. Unfortunately, patients are usually diagnosed in advanced stages of the disease - a time when available treatments may be ineffective. This delayed diagnosis is in part because current clinical criteria for sporadic CJD (sCJD) are based on a constellation of symptoms that often occur only late in a patient's course. Recently, neuroimaging has shown potential to improve the diagnosis of sCJD. Additionally, an elevated level of the protein 14-3-3 in the cerebrospinal fluid (CSF) has been touted as a sensitive and specific biomarker for sCJD and has recently been added to the diagnostic criteria for sCJD. Yet, no systematic study has been undertaken to identify the sensitivity and specificity of these two types of biomarkers in pathologically proven sCJD versus non-prion rapidly progressive dementias. The research goals of this proposal focus on identifying better ways for early diagnosis of CJD through a systematic analysis of clinical and imaging findings. The specific aims of this research will be as follows: 1 . To determine the sensitivity and specificity of diffusion-weighted imaging (DWI) sequence abnormalities in sporadic CJD, and 2. To determine the sensitivity and specificity of the CSF 14-3-3 protein as a marker for sporadic CJD. This research should provide new information on the early features of sCJD and thus facilitate diagnosis. In addition, this proposal will combine didactic teaching, mentoring, and clinical research experience to build upon Dr. Geschwind's training in behavioral neurology and neuroscience, thereby helping him to design and implement future clinical treatment studies for human prion disease and other dementias.