权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Novel Protein Biomarkers of Corticolimbic Pathophysiology in Lewy body Dementia

路易体痴呆皮质边缘病理生理学的新型蛋白质生物标志物

基本信息

批准号：
10704614
负责人：
ALLAN I LEVEY
金额：
$ 160.63万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704614
关键词：
Acceleration Address Alzheimer&apos s Disease Amygdaloid structure Anti-Anxiety Agents Antipsychotic Agents Automobile Driving Autopsy Biological Assay Biological Markers Blood Blood Vessels Brain Brain region Caregivers Cerebrospinal Fluid Cholinesterase Inhibitors Clinical Cognitive Collection DNA Data Delusions Dementia Dementia with Lewy Bodies Detection Deterioration Diagnostic Disease Distress Early Diagnosis Emotional Disturbance Endothelium Enrollment Fostering Functional disorder Future Health Care Costs Immune Immunologics Individual Knowledge Lewy Body Dementia Lewy Body Disease Link Longitudinal cohort Mass Spectrum Analysis Measures Mediating Medicine Memory Metabolism Methods Molecular Profiling Monitor Nerve Degeneration Network-based Neurodegenerative Disorders Neurons Paranoia Parkinson Disease Parkinson&apos s Dementia Pathway Analysis Pathway interactions Patients Pharmacotherapy Phenotype Plasma Progressive Disease Proteins Proteome Proteomics RNA Registries Research Sampling Schedule Serum Source Specificity Synapses Techniques Temporal Lobe Therapeutic Thinking Tissues Translating Validation Visual Hallucination Whole Blood aptamer biobank biomarker discovery biomarker panel biomarker validation brain based candidate identification candidate marker cohort effective therapy experience experimental study frontal lobe innovation multidisciplinary myelination neuropathology neuropsychiatry novel novel marker personalized care personalized therapeutic phenotypic data programs promoter protein biomarkers recruit risk stratification synuclein synucleinopathy targeted biomarker therapeutic biomarker treatment response validation studies

项目摘要

Project Summary Lewy body dementia (LBD), a class of disorders comprising Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), features aggressive cognitive and neuropsychiatric decline without cure or effective mitigating therapies. Driving the clinical challenges surrounding LBD is a poor understanding of the pathophysiology underlying its clinical deterioration and a desperate lack of diagnostic, progressive, and therapeutic biomarkers. Neuropathological evidence suggests that corticolimbic synucleinopathy is closely linked to the aggressive dementia of LBD and that effective biomarkers of cognitive and neuropsychiatric decline would necessarily reflect this corticolimbic dysfunction. Thus, our central hypothesis is that the corticolimbic LBD brain features regional and disease-specific alterations in neuronal and non-neuronal pathways reflected as unique protein signatures in CSF and plasma. To investigate this hypothesis, we will apply an integrated network-based proteomic pipeline across brain, cerebrospinal fluid (CSF), and plasma to identify LBD biofluid signatures anchored in corticolimbic pathophysiology. Our preliminary experience with this pipeline suggests it is a powerful promoter of multiplexed biomarker assays reflective of diverse brain-based dysfunction, including neuronal, glial, and endothelial pathophysiology. In addition to these proteomic experiments, we will also establish an Emory LBD registry under the Parkinson’s Disease Biomarker Program (PDBP) and utilize its clinical and biospecimen data to fuel proteomic validation studies and promote future LBD research. Our specific aims include 1) building a longitudinal PDBP registry for LBD, 2) defining the corticolimbic network proteome of LBD, 3) performing brain-biofluid proteomic integration to identify promising biofluid markers, and 4) longitudinal biofluid validation using targeted proteomic strategies. In addition to biospecimens collected in Aim 1, we will supplement these experiments using existing brain and biofluid samples housed in Emory Goizueta Alzheimer’s Disease Research Center biorepositories. Ultimately, our efforts to identify molecular signatures of cognitive and neuropsychiatric decline in LBD promise to discover novel biomarkers to enhance early diagnosis, disease monitoring, and gauging therapeutic response. Furthermore, such markers can serve as a necessary gateway to effective drug therapies for this devastating spectrum of neurodegenerative diseases.

项目总结