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: 8927088
• 负责人: Stephen N. Gomperts
• 金额: $ 21.75万
• 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/8927088
• 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; Health; 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; cognitive testing; cohort; corticobasal degeneration; data management; experience; hyperphosphorylated tau; in vivo; indexing; molecular pathology; motor impairment; neuroimaging; patient population; protein aggregate; 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（由申请方提供）：多种神经退行性脑部疾病，表现为帕金森综合征，包括特发性帕金森病、进行性核上性麻痹（PSP）和皮质基底节变性（CBD）。这些疾病在生活中的诊断和鉴别是困难的，特别是在其病程的早期。它们在神经病理学上通过沉积蛋白的化学组成和区域分布来区分，其中α-突触核蛋白是与PD相关的蛋白，而成对螺旋丝（PHF）tau在神经元缠结（NFT）和神经胶质簇中与PSP和CBD相关（它们被称为“tau病变”）。未来的治疗方法可能会根据每种疾病的潜在分子病理学进行调整。在生活中对这些疾病进行安全的分子诊断的能力将是一个重大的进步，与临床试验以及未来的分子治疗直接相关。最近开发的放射性药物称为[F18] T807结合脑PHF tau在活着的人，并可能是一个有价值的工具，建立一个分子诊断死前。在这个项目中，我们将评估用[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沉积与这些疾病中的临床损伤、皮质变薄和淀粉样蛋白负荷指数的关系。PSP、CBD和PD受试者将接受标准化神经系统检查、详细的神经心理学测试、[F18] T807 PET、[C11] PiB PET和结构脑MRI，并将与之前获得的年龄匹配HCS队列的临床和PET数据进行比较，以检验以下假设：（1）[F18] T807 PET将区分患有由PSP和CBD引起的疑似tau蛋白病的受试者与患有由特发性PD引起的疑似突触核蛋白病和HCS的受试者，其中PSP和CBD中的PHF tau负荷与这些疾病的已知NFT拓扑结构相关，（2）PHF tau负荷的分布将与PSP和CBD的特定运动和认知特征相关;和（3）区域PHF tau负荷将与皮质变薄相关。我们将使用淀粉样PET成像来排除伪装成PSP或CBD的AD。总之，这些努力将建立开发[F18] T807 PET成像作为帕金森病tau蛋白病的生物标志物和诊断工具的潜力。

项目成果

Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia.

• DOI: 10.1212/con.0000000000000309
• 发表时间: 2016-04-01
• 期刊: Continuum (Minneapolis, Minn.)
• 作者: Gomperts, Stephen N