Blood extracellular vesicles carrying synaptic function‐ and brain‐related proteins as potential biomarkers for Alzheimer's disease
Year: 2022
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Objective and accessible markers for Alzheimer's disease (AD) and other dementias are critically needed. METHODS: We identified NMDAR2A, a protein related to synaptic function, as a novel marker of central nervous system (CNS)-derived plasma extracellular vesicles (EVs) and developed a flow cytometry-based technology for detecting such plasma EVs readily. The assay was initially tested in our local cross-sectional study to distinguish AD patients from healthy controls (HCs) or from Parkinson's disease (PD) patients, followed by a validation study using an independent cohort collected from multiple medical centers (the Alzheimer's Disease Neuroimaging Initiative). Cerebrospinal fluid AD molecular signature was used to confirm diagnoses of all AD participants. RESULTS: Likely CNS-derived EVs in plasma were significantly reduced in AD compared to HCs in both cohorts. Integrative models including CNS-derived EV markers and AD markers present on EVs reached area under the curve of 0.915 in discovery cohort and 0.810 in validation cohort. DISCUSSION: This study demonstrated that robust and rapid analysis of individual neuron-derived synaptic function-related EVs in peripheral blood may serve as a helpful marker of synaptic dysfunction in AD and dementia.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.12723
Institutions: University of Washington, First Affiliated Hospital Zhejiang University, Zhejiang University, Sichuan University, West China Medical Center of Sichuan University, VA Puget Sound Health Care System, VA Northwest Network, University of Pennsylvania, University of California San Diego, Oregon Health & Science University, Portland VA Medical Center, VA Portland Health Care System
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: U.S. Department of Veterans Affairs, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Zhejiang University, National Institutes of Health, Fundamental Research Funds for the Central Universities, National Institute on Aging, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences
Awards: G1260893416, G1309020809, Peptide Biomarkers for Alzheimer Disease, G2344232696, Characterization and quantification of CNS cell specific extracellular microvesicles in blood, Peptide Biomarkers for Parkinson Disease, Extracellular vesicle transport of brain-derived proteins to the blood in Alzheimer disease, G4256132169, G4346867422, Exploring microvesicular transport across the blood-brain barrier as a novel a-synuclein clearance mechanism and source of Parkinson's disease biomarkers, Characterization and quantification of CNS cell specific extracellular microvesicles in blood, Targeted drug delivery via CNS cell specific exosomes in neurodegenerative diseases, MicroRNAs in CNS-derived extracellular microvesicles as peripheral blood biomarkers for Alzheimer disease, G7459421937, Alzheimer's Disease Research Center, G9000097468, G9000202291, G9000226643, G9000307348, G9000334473, Oregon Clinical and Translational Research Institute, University of Washington Alzheimer's Disease Research Center, G94711881
OpenAlex ID: W4283786823