Neuroimaging and Plasma Biomarkers Core

神经影像和血浆生物标志物核心

• 批准号: 10507632
• 负责人: Ilya M Nasrallah
• 金额: $ 88.61万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10507632
• 关键词: Alzheimer associated neurodegeneration; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; Biological Assay; Biological Markers; Biometry; Brain; Brain imaging; Cerebrovascular Circulation; Certification; Clinical; Cognition; Cognitive; Cohort Studies; Collaborations; Communities; Data; Dementia; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Evaluation; Feedback; Functional Magnetic Resonance Imaging; Glial Fibrillary Acidic Protein; Goals; Image; Impaired cognition; Laboratories; Lead; Light; Machine Learning; Magnetic Resonance Imaging; Maintenance; Manuals; Measurement; Measures; Methods; National Institute on Aging; Nature; Nerve Degeneration; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Study; Participant; Pennsylvania; Peripheral Nervous System Diseases; Persons; Plasma; Population; Positron-Emission Tomography; Prediabetes syndrome; Procedures; Protocols documentation; Quality Control; Recording of previous events; Research; Risk; Sampling; Site; Skeleton; Stroke; Training; Universities; Update; Water; adjudicate; adjudication; aged; aging brain; analysis pipeline; brain magnetic resonance imaging; cerebrovascular; cognitive testing; data infrastructure; diabetes prevention program; imaging biomarker; innovation; magnetic resonance imaging biomarker; molecular array; multimodality; neurofilament; neuroimaging; neuroinflammation; neuropathology; operation; peripherin; quality assurance; remediation; tau Proteins; therapeutic target; tool; vascular cognitive impairment and dementia

The goal of the Neuroimaging and Plasma Biomarkers Core (Biomarkers Core) of the Diabetes Prevention Program Outcomes Study (DPPOS) Alzheimer’s disease (AD) and AD related dementias (ADRD) project is to conduct all training, certification, quality assurance (QA) and quality control (QC) activities related to brain magnetic resonance imaging (MRI), brain amyloid positron emission tomography (PET) imaging, and plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation. In addition, the Biomarkers Core will support the Biostatistics and Data Infrastructure Core (Data Core) and the Cognitive Assessment and Adjudication Core (Cognition Core) to conduct analyses of neuroimaging and plasma biomarkers as independent outcomes and in combination with cognitive outcomes, following the 2018 National Institute on Aging (NIA)/Alzheimer’s Association (AA) research framework. The Biomarkers Core will harmonize methods for the study of the vascular contribution to cognitive impairment and dementia (VCID), with the MarkVCID consortium. Determination of biomarkers underlying AD/ADRD is critical to understanding disease mechanisms and potential therapeutic targets underlying cognitive impairment in persons with pre-diabetes (PreD) and type 2 diabetes (T2D), who represent over half of the US population aged 60 years and older at risk for cognitive impairment. We herein propose to perform multimodality MRI, including structural imaging, diffusion tensor imaging (DTI), cerebral blood flow, and functional MRI and amyloid PET in 650 participants representative of the DPPOS cohort in one wave that will span the two proposed waves of cognitive assessments. We also propose to conduct ascertainment of plasma biomarkers of amyloid (Aß42, Aß40), tau (ptau-181), neurodegeneration (neurofilament light [NfL]), neuroinflammation (glial fibrillary acidic protein [GFAP]), and peripheral neuropathy (peripherin) in all participants concurrent with the first wave of cognitive assessments, and two previous waves, 5 years apart, from stored samples. The Biomarkers Core is led by Ilya Nasrallah at the University of Pennsylvania, who will lead all brain imaging core activities, and Henrik Zetterberg at the University of Gothenburg, who will lead all plasma biomarker core activities. The Biomarkers Core will achieve its goals through the following specific aims: (1). To develop, maintain, update, and implement protocols and QA/QC procedures related to brain MRI and amyloid PET; (2) Develop an imaging pipeline for evaluation of AD and VCID biomarkers; (3) Conduct assays of Aß42, Aß40, ptau-181, NfL, GFAP, and peripherin, using Single Molecular Array (Simoaä) at the central plasma biomarkers laboratory located at the University of Gothenburg; (4) Conduct exploratory analyses relating brain imaging and plasma biomarkers data in collaboration with the Data and Clinical Cores; (5) In collaboration with the Data, Cognition, and Clinical Operations and Procedures Core (Clinical Core), further adjudicate MCI and dementia using AD/ADRD biomarkers and assist with analyses involving neuroimaging and plasma biomarker data; (6) Assist the Clinical Core in the return of results of amyloid positivity to participants who so request.

糖尿病预防的神经影像学和血浆生物标志物核心（生物标志物核心）的目标 项目结果研究（DPPOS）阿尔茨海默病（AD）和AD相关痴呆（ADRD）项目是为了 开展与大脑相关的所有培训、认证、质量保证（QA）和质量控制（QC）活动 磁共振成像（MRI）、脑淀粉样蛋白正电子发射断层扫描（PET）成像和血浆 淀粉样蛋白、tau、神经变性和神经炎症的生物标志物。此外，生物标志物核心将 支持生物统计和数据基础设施核心（数据核心）和认知评估， 裁定核心（认知核心），将神经影像学和血浆生物标志物作为独立分析进行分析 结果，并结合认知结果，继2018年国家老龄化研究所 (NIA)阿尔茨海默氏症协会（AA）研究框架。生物标志物核心将协调 与MarkVCID联盟共同开展的血管对认知障碍和痴呆（VCID）的影响研究。 确定AD/ADRD潜在的生物标志物对于了解疾病机制和潜在的 糖尿病前期（PreD）和2型糖尿病患者认知障碍的潜在治疗靶点 (T2D)这些人占美国60岁及以上人口的一半以上，有认知障碍的风险。 我们在此建议进行多模态MRI，包括结构成像，扩散张量成像（DTI）， 脑血流量、功能性MRI和淀粉样蛋白PET， 在一个浪潮中，将跨越两个拟议的认知评估浪潮。我们还建议进行 淀粉样蛋白（A β 42，A β 40）、tau（ptau-181）、神经变性（神经丝）的血浆生物标志物的确定 光[NfL]）、神经炎症（胶质细胞酸性蛋白[GFAP]）和周围神经病变（外周蛋白）。 参与者同时进行第一波认知评估，以及前两波，间隔5年， 从储存的样本中。生物标志物核心由宾夕法尼亚大学的Ilya Nasrallah领导，他将 领导所有的大脑成像核心活动，以及哥德堡大学的亨利克·泽特伯格，他将领导所有的 血浆生物标志物核心活性。生物标志物核心将通过以下具体目标实现其目标： （一）.制定、维护、更新和实施与脑部MRI相关的方案和QA/QC程序， 淀粉样蛋白PET;（2）开发用于评估AD和VCID生物标志物的成像管道;（3）进行 A β 42、A β 40、ptau-181、NfL、GFAP和外周蛋白，使用单分子阵列（Simoaä）在中央血浆中 位于哥德堡大学的生物标志物实验室;（4）进行与脑 与Data and Clinical Cores合作提供成像和血浆生物标志物数据;（5）与 数据、认知、临床操作和程序核心（临床核心），进一步裁定MCI， 使用AD/ADRD生物标志物进行痴呆分析，并协助涉及神经成像和血浆生物标志物的分析 （6）协助临床中心将淀粉样蛋白阳性的结果返回给要求返回的参与者。