Biomarkers of Inflammation, Neurodegeneration and Age-Associated Cognitive Impairment

炎症、神经退行性变和年龄相关认知障碍的生物标志物

• 批准号: 10505955
• 负责人: Alison Ruth Weiss
• 金额: $ 19.65万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10505955
• 关键词: Address; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; American; Animal Model; Animals; Anti-Inflammatory Agents; Area; Astrocytes; Atrophic; Behavior; Biological Assay; Biological Markers; Biometry; Brain; Cells; Cerebrospinal Fluid; Clinical; Cognition; Complex; Corpus striatum structure; Data; Dementia; Diffuse; Diffusion; Disease model; Exhibits; Foundations; Future; Gliosis; Goals; Human; Image; Impaired cognition; Independent Living; Inflammation; Inflammatory; Infrastructure; Light; Longevity; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Measures; Mediating; Memory impairment; Microglia; Modeling; Monkeys; Morbidity - disease rate; Morphology; Nerve Degeneration; Neurites; Neurodegenerative Disorders; Neuroimmune; Neurosciences; Pathway interactions; Patients; Pattern; Play; Population; Positron-Emission Tomography; Pre-Clinical Model; Process; Proteomics; Public Health; Refractory; Research; Research Technics; Resolution; Resources; Role; Sampling; Screening procedure; Sensitivity and Specificity; Short-Term Memory; Signal Transduction; Symptoms; Technology; Testing; Thalamic structure; Therapeutic; Tissue Banks; Work; age related; age related neurodegeneration; aged; base; brain magnetic resonance imaging; brain morphology; cerebral atrophy; cognitive testing; density; gray matter; healthy aging; histological studies; innovation; long-term sequelae; middle age; minimally invasive; morphometry; multimodal neuroimaging; multimodality; neuroinflammation; novel; novel marker; pathological aging; potential biomarker; prevent; programs; protein biomarkers; therapeutic target; therapeutically effective; white matter; young adult

Project Summary With a rapidly increasing population of aging Americans, cognitive impairment associated with normative aging, or neurodegenerative diseases including Alzheimer's Disease and other related dementias (ADOD), will place increasing burden on our public health infrastructure. Unfortunately, few effective screening tools or therapeutic strategies exist, and many patients are refractory to treatment. Recent studies suggest that altered neuroinflammatory signaling may play an important early role in normative aging, and in ADOD, but the mechanisms by which the complex interaction of pro- and anti-inflammatory pathways change over the lifespan, or modulate cognition, are unclear. For this reason, studies using animal models that closely recapitulate normative human aging, but on a shorter timescale, are desperately needed to test the overall hypothesis that rising levels neuroinflammation occurs prior to neurodegeneration and age- related cognitive impairment, and represent a potential early marker. To address this need, the central goal of my project will be to query the relationship between markers of neuroinflammation with brain morphology and microstructure, and cognition, in naturally-occurring rhesus macaque model of age-related cognitive impairment. I will use a combination of ultra-sensitive cerebral spinal fluid (CSF) protein biomarker assays, Positron Emission Tomography (PET) imaging of activated astrocytes and microglia, high-resolution Magnetic Resonance Imaging (MRI) of brain morphology and microstructure, and cognitive assessment for spatial working memory. The strength of these studies lies in their potential to characterize novel biomarkers of neuroinflammatory and neurodegenerative pathways that are associated with memory impairment, and to identify new potential biomarkers that can serve as screening tools and future therapeutic targets.

项目总结