Graduation Year
2026
Date of Submission
12-2025
Document Type
Open Access Senior Thesis
Degree Name
Bachelor of Arts
Department
Neuroscience
Reader 1
Melissa Coleman
Reader 2
David Wang
Rights Information
© 2026 Kate E Huh
Abstract
Vascular Cognitive Impairment and Dementia (VCID) arises from progressive disruption of neurovascular unit (NVU) function, yet existing blood-based biomarkers lack the cellular resolution required to detect early, cell type-specific injury. This study aimed to define neuron-, glial-, and endothelial-specific molecular signatures of VCID using a minimally invasive plasma-based approach. A combinatorial extracellular vesicle (EV) isolation platform integrating nanoacoustic ultrafiltration with sequential immunoprecipitation was applied to isolate NVU-derived EV subpopulations from the plasma of healthy older adults and individuals with VCID. This workflow enabled high-purity recovery of cell type-specific EVs from small plasma volumes and supported integrated biophysical and proteomic characterization. VCID plasma exhibited reduced EV yield and greater heterogeneity in surface charge, alongside increased membrane irregularities visualized by cryo-electron microscopy. Overall vesicle size and morphology remained consistent with typical circulating EV size distributions. All NVU-derived EV subpopulations were additionally recovered at lower yields in VCID. Proteomic profiling demonstrated a marked loss of protein diversity in VCID EV subpopulations and coordinated redistribution of inflammatory, lipid-associated, and structural proteins between plasma and NVU-derived EVs. Healthy NVU EVs showed greater representation of metabolic, oxidative, and redox-regulating functions, whereas VCID EVs acquired cargos linked to cytoskeletal remodeling, protease inhibition, autophagy, immune activation, and dysregulated ion homeostasis. These findings establish plasma-derived NVU EV profiling as a powerful, minimally invasive approach for detecting cell type-specific molecular signatures of neurovascular dysfunction. This platform provides a foundation for EV biomarker development and mechanistic studies capable of resolving early neurovascular impairment.
Recommended Citation
Huh, Kate E., "Plasma-Derived Neurovascular Extracellular Vesicle Signatures Reveal Vascular Cognitive Impairment and Dementia-Linked Pathology" (2026). CMC Senior Theses. 4255.
https://scholarship.claremont.edu/cmc_theses/4255
