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A platform for cell type-level transcriptomic, epigenomic and spatial interrogation of Alzheimer's disease

阿尔茨海默氏病细胞类型水平转录组、表观基因组和空间研究的平台

基本信息

批准号：
10375357
负责人：
Jennie Leigh Close
金额：
$ 959.08万
依托单位：
ALLEN INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10375357
关键词：
Adult Affect Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease pathology Anatomy Architecture Autopsy BRAIN initiative Basic Science Biological Assay Brain Brain Mapping Cell Nucleus Cells Cellular Neurobiology Characteristics Clinical Collaborations Collection Communication Communities Complex Data Data Collection Data Set Deposition Disease Disease Resistance Epigenetic Process Foundations Future Generations Genetic Genetic Transcription Genomic approach Genomics Goals Health Histology Human Infrastructure Institutes Leadership Link Methodology Methods Modality Modernization Molecular Molecular Neurobiology Molecular Profiling Neuroglia Neurons Organ Pathogenesis Pathologic Pathology Pathway interactions Phase Preparation Progress Reports Proteins RNA Research Research Personnel Resistance Resolution Science Severities Standardization Strategic Planning Techniques Technology Tissues Universities Visualization Washington base brain research brain tissue cell type clinical phenotype cohort computerized data processing data access data management data portal data resource design disorder subtype diverse data epigenome epigenomics human tissue improved insight member molecular pathology molecular scale neuropathology next generation organizational structure single cell analysis tissue resource tool transcriptome transcriptomics

项目摘要

ABSTRACT (OVERALL) Our understanding of the neuropathology in Alzheimer’s disease is crude and largely centered on characteristic deposition of a few pathological proteins. Catalyzed by the BRAIN Initiative, a new generation of molecular tools to characterize the transcriptome, epigenome and spatial organization of single cells in complex brain tissues is rapidly revolutionizing our understanding of the diversity of cell types and their selective genetic profiles. These tools are applicable to postmortem human brain tissues and promise to expand our understanding of the core cellular and molecular correlates and mechanisms underlying Alzheimer’s disease. The goal of the proposed Center is to bring together experts in Alzheimer’s disease research and large-scale molecular/anatomical brain mapping to modernize Alzheimer’s disease tissue banking methods, and to combine traditional and quantitative neuropathology with emerging single nucleus transcriptomics, single nucleus epigenomics and spatial transcriptomics technologies. Applied to clinically typical Alzheimer’s cases of varying severity in an iterative and adaptive design, these techniques are expected to identify increasingly refined molecular pathways associated with specific neuronal and non-neuronal cell types and yield valuable insights into cell-type selective vulnerability or resistance to pathology. This increased resolution of AD pathology in terms of cell types and molecular pathways should provide mechanistic insights and hypotheses on disease initiation and progression, which we aim to use to catalyze the AD research community through the creation of an open access data resource linked with other large-scale brain mapping efforts. This Center framework is designed to be extensible to additional data modalities and technological advances as well as broader cohorts representing Alzheimer’s disease subtypes and Alzheimer’s disease related disorders in the future.

文摘(整体)