SUMMARY
The research of Yang You, Ph.D., investigates how cell type-specific extracellular vesicles (EVs), glial biology and genetic risk factors contribute to Alzheimer's disease, related tauopathies and neuropsychiatric disorders. By integrating advanced omics technologies, neural models derived from human induced pluripotent stem cells (iPSC), and in vivo approaches, Dr. You defines EV-mediated mechanisms of neurodegeneration and develops EV-based biomarkers with potential for clinical translation.
A central focus of Dr. You's research is characterizing neural cell type-specific EV proteomes and their roles in Alzheimer's disease pathogenesis. His work has mapped distinct EV protein networks from human iPSC-derived neurons, astrocytes, microglia and oligodendrocytes, revealing astrocyte EV signatures linked to disease progression. He also identified ATP1A3 as a reliable neuron-specific EV marker, enabling the isolation of neuronal EVs from the human brain and biofluids. This has allowed for more precise analysis of neuron-derived cargo and supports biomarker discovery efforts.
Focus areas
- Cell type-specific EV biomarkers for neurodegenerative and psychiatric disorders. Dr. You's team is developing EV-based biomarker panels for a range of neurological and psychiatric conditions. These include Alzheimer's disease, tauopathies (such as progressive supranuclear palsy, corticobasal degeneration and related frontotemporal lobar degeneration syndromes), Lewy body dementia and major depressive disorder. Building on the identification of ATP1A3 as a neuron-enriched EV marker, the group has advanced purification methods to isolate neuron-enriched EVs from brain, cerebrospinal fluid and plasma. The team applies state-of-the-art DIA-MS proteomics, machine learning and network analysis to define disease-associated cargo signatures, which are then translated into scalable immunoassay platforms to enable diagnosis, disease stratification and treatment monitoring.
- Mechanistic dissection of EV-mediated tau pathology. Using human iPSC-derived neurons, astrocytes, microglia and 3D brain organoids, Dr. You studies how EV-mediated intercellular communication drives tau pathology in Alzheimer's disease. By combining CRISPR-engineered iPSC lines, comprehensive EV profiling and functional assays, his team seeks to uncover EV-dependent mechanisms that can be targeted to slow or prevent tau-driven neurodegeneration in Alzheimer's disease and related tauopathies.
- The role of genetic risk factors in Alzheimer's disease pathogenesis. Dr. You's research focuses on the role of AKAP9, a signaling scaffold implicated in Alzheimer's disease risk and in regulating tau phosphorylation, oxidative stress and neuronal vulnerability. Using African American iPSC-derived models and CRISPR editing to introduce or remove AKAP9 variants, Dr. You's group investigates how AKAP9 shapes kinase/phosphatase signaling, tau pathology and EV cargo. The team is exploring AKAP9-targeting strategies in vivo — such as antisense oligonucleotides — in tauopathy models to evaluate their therapeutic potential.
Significance to patient care
Dr. You is working to create simple, noninvasive tests that can detect early signs of brain and mental health conditions. By studying tiny particles called extracellular vesicles, his team is finding new ways to understand how disorders such as Alzheimer's disease and depression develop. The goal is to turn these discoveries into tools that help healthcare professionals diagnose sooner, choose the right treatments, and improve quality of life for patients and families.
Professional highlights
- Member, Editorial Board, Extracellular Vesicles and Circulating Nucleic Acids, 2022-present.
- Eugene U. and Mary F. Frey Family Career Development Award in Neurodegenerative Diseases, Mayo Clinic, 2025.
- International Society for Extracellular Vesicles:
- Co-chair, ISEV2025 — 14th Annual Meeting of the International Society for Extracellular Vesicles, 2025.
- Outstanding Oral Presentation Award, 2021.
- Young Investigator Award, 2021.
- Recipient, Pathway and Pipeline Grant for biomarker development, CurePSP, 2024.
- FENS–CNS Young Researchers Exchange Support Programme, Federation of European Neuroscience Societies, 201.