Identification and characterization of molecular subtypes of Alzheimer's disease associated with cognitive function through cross-omics data integration

通过跨组学数据整合识别和表征与认知功能相关的阿尔茨海默病分子亚型

• 批准号: 10722083
• 负责人: Abdallah M Eteleeb
• 金额: $ 14.86万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722083
• 关键词: Address; Advisory Committees; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer' s disease therapeutic; Alzheimer’s disease biomarker; Animal Model; Autopsy; Award; Biological; Biological Markers; Biology; Blood; Brain; Brain region; Cerebrospinal Fluid; Chromatin Remodeling Factor; Clinical; Clinical Trials; Cognitive; DNA Methylation; Data; Data Set; Dedications; Dementia; Dementia with Lewy Bodies; Development; Diagnosis; Disease; Disease Progression; Doctor of Philosophy; Educational workshop; Encapsulated; Environment; Epigenetic Process; Feedback; Foundations; Funding; Future; Genes; Genetic; Genomics; Goals; Heterogeneity; Human; Impaired cognition; Individual; Journals; K-Series Research Career Programs; Knowledge; Leadership; Learning; Machine Learning; Malignant Neoplasms; Medical Research; Mentors; Mentorship; Modality; Modeling; Molecular; Molecular Profiling; Multiomic Data; Nerve Degeneration; Neurodegenerative Disorders; Neurology; Neurosciences; Parkinson' s Dementia; Pathologic; Pathology; Pathway interactions; Pharmaceutical Preparations; Proteomics; Regulation; Reporting; Research; Risk; Techniques; Testing; Training; Training Programs; United States; Universities; Untranslated RNA; Validation; Washington; Work; biological systems; biomarker identification; blood-based biomarker; cerebral atrophy; clinically relevant; cognitive function; cohort; data integration; design; digital; disorder subtype; effective therapy; experience; genetic risk factor; histone modification; human old age (65+); illness length; improved; innovation; insight; medical schools; model organism; molecular marker; molecular subtypes; mouse model; multiple datasets; neuropathology; novel; novel therapeutics; patient subsets; potential biomarker; precision medicine; sex; skills; spatiotemporal; specific biomarkers; symposium; tau Proteins; trait; transcriptomics

Project Summary/Abstract The goal of this mentored career development award is to provide a robust course of training in the biology of neurodegeneration and aging for Dr. Eteleeb, Ph.D., a candidate with extensive experience in genomics, omics, and machine learning, to enable his transition to research independence. Washington University School of Medicine is a nationally recognized leader in medical research and provides an outstanding environment for the candidate’s training with world-renowned figures in the fields of Alzheimer’s disease (AD) and aging. This proposal will be conducted under the mentorship of an excellent interdisciplinary team of leaders with extensive and complementary sets of expertise in AD, aging, neuroscience, genetics, and cross-omics who are dedicated to support Dr. Eteleeb in completing his research and training goals proposed in this award. With the guidance of this team, Dr. Eteleeb will pursue a rigorous training program to address gaps in his knowledge and allow him to accomplish the aims of this K25 award. The training objectives will focus on Dr. Eteleeb’s transition into the field of AD and aging and include 1) acquire a strong foundation in neurology, clinical, and neuropathology aspects of AD and related dementias, 2) learn and employ novel ways to identify molecular subtypes of AD and specific biomarkers associated with cognitive function, followed by validation techniques in humans and model organisms, 3) gain in-depth understanding of the genetic and epigenetic factors affecting AD molecular subtypes, and 4) develop leadership and professional skills for leading an independent lab focused on transitional research in AD and aging. These objectives will be accomplished through courses, workshops, seminars, journal clubs, conferences, and feedback from the advisory committee. The primary objective of the proposed research is to identify and characterize molecular subtypes of AD associated with cognitive function by employing an innovative approach that combines cross-omics and machine learning. AD is a heterogeneous neurodegenerative disorder affecting over 50 million individuals worldwide. One critical and often overlooked factor impeding development of effective treatment for AD is the clinical and molecular heterogeneity among AD patients. Cross-omics approaches integrate heterogeneous molecular profiles to study not only how these profiles change in AD, but also uncover relationships and correlations between biological molecules. The specific proposed research aims are 1) identify and characterize cross-omics AD molecular subtypes associated with cognitive function conserved across cohorts and brain regions, 2) Determine whether molecular subtypes are specific to AD or present in other neurodegenerative disorders, and 3) identify CSF/blood-based biomarkers from AD molecular subtypes. The results will reveal insights into AD subpopulations and identify AD molecular subtypes, pathways, and biomarkers, which could lead to new pathways for implementing precision medicine and developing novel therapeutics for AD. Successful completion of this award will facilitate future independent funding to leverage cross-omics to deepen our understanding of the molecular mechanisms of AD progression.

项目总结/文摘