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和血浆生物标志物核心（Biomarkers Core）的目标 项目成果研究 (DPPOS) 阿尔茨海默病 (AD) 和 AD 相关痴呆 (ADRD) 项目旨在 进行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蛋白、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）以及认知评估和 裁决核心（认知核心）对神经影像和血浆生物标志物进行独立分析 继 2018 年国家老龄化研究所之后，结果并与认知结果相结合 (NIA)/阿尔茨海默病协会 (AA) 研究框架将协调方法。 与 MarkVCID 联盟合作研究血管对认知障碍和痴呆 (VCID) 的影响。 确定 AD/ADRD 的生物标志物对于了解疾病机制和潜力至关重要 糖尿病前期 (PreD) 和 2 型糖尿病患者潜在认知障碍的治疗目标 (T2D)，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)、 代表 DPPOS 队列的 650 名参与者的脑血流量、功能性 MRI 和淀粉样蛋白 PET 我们还建议在跨越两波拟议的认知评估的一波中进行。 确定淀粉样蛋白 (Aß42、Aß40)、tau (ptau-181)、神经变性（神经丝）的血浆生物标志物 光 [NfL]）、神经炎症（胶质纤维酸性蛋白 [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，以及相隔 5 年的前两波认知评估， 生物标记核心由宾夕法尼亚大学的 Ilya Nasrallah 领导，他将 领导所有脑成像核心活动，哥德堡大学的 Henrik Zetterberg 将领导所有活动 血浆生物标志物核心活动。生物标志物核心将通过以下具体目标实现其目标： (1) 制定、维护、更新和实施与脑 MRI 相关的协议和 QA/QC 程序。 淀粉样蛋白 PET；(2) 开发用于评估 AD 和 VCID 生物标志物的成像流程；(3) 进行以下分析： Aß42、Aß40、ptau-181、NfL、GFAP 和外周蛋白，在中心等离子体处使用单分子阵列 (Simoaä) 位于哥德堡大学的生物标志物实验室；（4）进行与大脑相关的探索性分析 (5) 与数据和临床核心合作，结合影像和血浆生物标志物数据； 数据、认知、临床操作和程序核心（临床核心），进一步裁定 MCI 和 使用 AD/ADRD 生物标志物治疗痴呆症并协助涉及神经影像和血浆生物标志物的分析 (6) 协助临床核心将淀粉样蛋白阳性结果返回给有要求的参与者。