PET imaging of hyperphosphorylated tau differentiates PSP and CBD from PD

过度磷酸化 tau 蛋白的 PET 成像可区分 PSP 和 CBD 与 PD

• 批准号: 8808816
• 负责人: Stephen N. Gomperts
• 金额: $ 26.1万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8808816
• 关键词: Address; Alzheimer' s Disease; Amyloid; Autopsy; Basal Ganglia; Binding; Biological Markers; Biometry; Brain; Brain Diseases; Brain Stem; Brain scan; Chemicals; Classification; Clinical; Clinical Trials; Cognitive; Data; Deposition; Diagnosis; Diagnostic; Diagnostics Research; Disease; Enrollment; Environment; Executive Dysfunction; Functional disorder; Future; Globus Pallidus; Goals; Human; Impaired cognition; Impairment; Interdisciplinary Study; Label; Lesion; Levodopa; Lewy Bodies; Life; Magnetic Resonance Imaging; Measures; Medial; Molecular; Molecular Diagnosis; Motor; Movement Disorders; Nerve Degeneration; Neurites; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurologic Examination; Neuropsychological Tests; Neuropsychology; Parkinson Disease; Parkinsonian Disorders; Pathologic; Pathology; Patients; Positron-Emission Tomography; Progressive Supranuclear Palsy; Proteins; Radiopharmaceuticals; Recruitment Activity; Research; Research Personnel; Research Project Grants; Resources; Secure; Severities; Study Subject; Syndrome; TNFRSF5 gene; Tauopathies; Testing; Thalamic structure; Therapeutic; Work; aged; alpha synuclein; base; cohort; corticobasal degeneration; data management; experience; hyperphosphorylated tau; in vivo; indexing; molecular pathology; motor impairment; neuroimaging; patient population; protein aggregate; public health relevance; synuclein; synucleinopathy; tau Proteins; tau aggregation; tool

DESCRIPTION (provided by applicant): Multiple neurodegenerative brain disorders present with parkinsonism, including idiopathic Parkinson disease, Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). Diagnosis and differentiation of these disorders in life is difficult, especially early in their course. They are distinguished neuropathologically by he chemical composition and regional distribution of deposited proteins, with alpha-synuclein the protein associated with PD, and paired helical filament (PHF) tau in neurofibrillary tangles (NFT) and glial tufts associated with PSP and CBD (for which they are known as 'tauopathies'). Future therapeutics will likely be tailored to the underlying molecular pathology of each disease. The capacity to make a secure molecular diagnosis of these illnesses in life would be a significant advance, with immediate relevance for clinical trials as well as for future molecularly-based therapies. A recently developed radiopharmaceutical known as [F18] T807 binds brain PHF tau in living humans, and may be a valuable tool for establishing a molecular diagnosis antemortem. In this project, we will evaluate whether PHF tau deposition measured with [F18] T807 differentiates PSP and CBD from PD and healthy control subjects (HCS); and explore the relation of PHF tau deposition to indices of clinical impairment, cortical thinning, and amyloid burden in these disorders. Subjects with PSP, CBD, and PD will undergo standardized neurological examination, detailed neuropsychological testing, [F18] T807 PET, [C11] PiB PET, and structural brain MRI, and will be compared to previously acquired clinical and PET data of an aged-matched HCS cohort to test the following hypotheses: (1) [F18] T807 PET will differentiate subjects with suspected tauopathy due to PSP and CBD from subjects with suspected synucleinopathy due to idiopathic PD and from HCS, with PHF tau burden in PSP and CBD correlating with the known NFT topology of those diseases, (2) the distribution of PHF tau burden will correlate with specific motor and cognitive features of PSP and CBD; and (3) regional PHF tau burden will be associated with cortical thinning. We will use amyloid PET imaging to exclude AD masquerading as PSP or CBD. Together, these efforts will establish the potential for developing [F18] T807 PET imaging as a biomarker and diagnostic tool for the parkinsonian tauopathies.

描述（由申请人提供）：多种神经退行性脑部疾病，帕金森病，包括特发性帕金森氏病，进行性核上性核瘫痪（PSP）和皮质性龙质变性（CBD）。这些生活中这些疾病的诊断和差异很困难，尤其是在他们的课程初期。它们通过He化学成分和沉积蛋白的区域分布与神经病理学区别，与α-核蛋白与PD相关的蛋白质以及在神经纤维缠结（NFT）中配对的螺旋细丝（PHF）TAU与PSP和CBD相关的神经纤维缠结（NFT）中（已知与PSP和CBD相关的蛋白质）。未来的治疗剂可能会根据每种疾病的基本分子病理量身定制。对生活中这些疾病进行安全分子诊断的能力将是一个重大进步，与临床试验以及未来的基于分子的疗法有关立即相关。最近开发的被称为[F18] T807的放射性药物在活着的人类中结合了脑PHF tau，并且可能是建立分子诊断动物质量的有价值的工具。在这个项目中，我们将评估使用[F18] T807测量的PHF TAU沉积是否将PSP和CBD与PD和健康对照受试者（HCS）区分开来；并探索PHF TAU沉积与这些疾病中临床障碍，皮质稀疏和淀粉样蛋白负担的指标的关系。患有PSP，CBD和PD的受试者将接受标准化的神经系统检查，详细的神经心理学测试，[F18] T807 PET，[C11] PIB PET和结构性大脑MRI，并将与先前获得的临床和PET数据进行比较，以测试以下较高的HC与以下测试的PETERTER sOVIATION sOVIATION sOVIENTIRS：（1）[1）[1）[F18] [F18] [F1）由于PSP和CBD引起的TAUOPATHY受试者的PSP和CBD引起的棘突性PD和HCS引起的脊髓病，PSP中的PHF Tau负担和CBD与这些疾病的已知NFT拓扑相关，（2）PHF TAU负担的分布将与特定的运动和认知功能相关。 （3）区域PHF Tau负担将与皮质稀疏有关。我们将使用淀粉样蛋白宠物成像排除伪装成PSP或CBD的广告。这些努力将共同开发[F18] T807 PET成像作为帕金森氏症tauopathies的生物标志物和诊断工具的潜力。