Validation of Novel Plasma Biomarkers for Mixed Etiology Dementia

混合病因痴呆的新型血浆生物标志物的验证

• 批准号: 10643885
• 负责人: Lawren VandeVrede
• 金额: $ 20.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643885
• 关键词: Address; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease blood test; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Area Under Curve; Autopsy; Behavioral; Benchmarking; Biological Assay; Biological Markers; Blood; Blood Tests; California; Cerebrospinal Fluid; Clinic; Clinical; Clinical Trials; Clinical Trials Design; Clinical dementia rating scale; Communities; Data; Dementia; Development Plans; Diagnostic; Disease; Disease Progression; Early Diagnosis; Environment; Etiology; Frontotemporal Lobar Degenerations; Future; Generations; Goals; Image; Isomerism; K-Series Research Career Programs; Light; Liquid substance; Measures; Mentors; Mentorship; Modality; Nerve Degeneration; Neurodegenerative Disorders; Neurologist; Observational Study; PET positivity; Parents; Participant; Pathology; Pathway interactions; Patient Recruitments; Patient Representative; Patients; Performance; Physicians; Plasma; Population; Population Heterogeneity; Positron-Emission Tomography; Public Health; Race; Receiver Operating Characteristics; Research; Sampling; San Francisco; Scanning; Scientist; Screening procedure; Senile Plaques; Site; Specimen; Sum; Syndrome; Testing; Therapeutic; Time; Training; Translations; Underrepresented Minority; Universities; Validation; biomarker discovery; biomarker validation; career; career development; clinical application; clinical diagnosis; clinical phenotype; clinically relevant; cohort; comorbidity; cost; design; diagnostic accuracy; diagnostic screening; diagnostic strategy; diagnostic tool; improved; mixed dementia; multidisciplinary; multimodality; neurofilament; neuroimaging; neuroimaging marker; neuropathology; novel; novel marker; patient population; population based; professor; prospective; racial diversity; racial population; recruit; research study; screening; tau Proteins; tau aggregation; tau-1; tool

PROJECT SUMMARY In this K23 career development award, Dr. Lawren VandeVrede, a behavioral neurologist and Assistant Professor at the University of California, San Francisco (UCSF), will obtain training in the use, validation, and translation of multimodal biomarkers for Alzheimer's Disease (AD) and related dementias (ADRD). This project supports his long-term career goal to become a leader in ADRD biomarker translation and novel clinical trial design, and to establish a lab that paves the way for a new generation of clinical trials that will evaluate and refine treatment approaches for patients with dementia. Through this K23 and the enriched multidisciplinary training environment at UCSF, Dr. VandeVrede aims to accomplish the following specific training goals: 1) gain expertise in the use of clinical, neuropathological, biofluid, and neuroimaging biomarker modalities, 2) develop specialized proficiency in validation of novel plasma AD biomarkers benchmarked to gold-standard neuropathology and current-generation positron emission tomography (PET) neuroimaging, and (3) develop a pathway for translation of biomarkers into clinical settings for use as large-scale screening and diagnostic tools for ADRD. To achieve these goals, Dr. VandeVrede has assembled an exemplary mentorship team, including his primary mentor, Dr. Adam Boxer, a leader in ADRD fluid biomarker discovery and clinical trial design, and co-mentors, Drs. Lea Grinberg and Gil Rabinovici, experts in ADRD neuropathology and PET imaging respectively. In addition, he has two collaborators with expertise in relevant plasma biomarker assays, Drs. Michelle Mielke and Jeff Dage, and a biostatistician, Dr. John Kornak, with significant expertise in ADRD biomarker validation and clinical trial design. The overarching goal of the project is to better characterize the diagnostic performance of several novel AD plasma biomarkers in an important and clinically relevant patient population: mixed etiology dementia. The central rationale is that blood tests are critically needed for large-scale diagnostic screening for AD, and whereas several proposed plasma biomarkers in the research world show promise as future clinical tools, key validation data and comparisons between biomarkers are missing in real-world dementia patients with mixed etiology. Therefore, in this project, novel plasma biomarkers of ADRD will be validated (1) in Aim I against gold-standard neuropathology in autopsy cohorts that include comorbid and alternative neuropathologies; (2) in Aim II against current-generation PET biomarkers in several prospective observational studies that include early, mixed, and atypical clinical phenotypes; and (3) in Aim III in a large community-based study specifically designed to recruit under-represented minorities. This project provides critical data that would support translation of these specific blood tests into clinical use, and establishes a platform for future discovery and validation projects for ADRD biomarkers.

项目总结

项目成果

Hepatic and renal function impact concentrations of plasma biomarkers of neuropathology.

• DOI: 10.1002/dad2.12321
• 发表时间: 2022
• 期刊: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
• 影响因子: 5.3
• 作者: Berry, Kacey;Asken, Breton M.;Grab, Joshua D.;Chan, Brandon;Lario Lago, Argentina;Wong, Randi;Seetharaman, Srilakshmi;LaHue, Sara C.;Possin, Katherine L.;Rojas, Julio C.;Kramer, Joel H.;Boxer, Adam L.;Lai, Jennifer C.;VandeVrede, Lawren
• 通讯作者: VandeVrede, Lawren

Uncovering spatiotemporal patterns of atrophy in progressive supranuclear palsy using unsupervised machine learning.

• DOI: 10.1093/braincomms/fcad048
• 发表时间: 2023
• 期刊: Brain communications
• 影响因子: 4.8