ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids
You, Yang Zhang, Zhengrong Sultana, Nadia Ericsson, Maria Martens, Yuka A Sun, Min Kanekiyo, Takahisa Ikezu, Seiko Shaffer, Scott A Ikezu, Tsuneya
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Keywords
Subject Area
Files
Embargo Expiration Date
Link to Full Text
Abstract
Neuron-derived extracellular vesicles (NDEVs) are potential biomarkers of neurological diseases although their reliable molecular target is not well established. Here, we demonstrate that ATPase Na/K transporting subunit alpha 3 (ATP1A3) is abundantly expressed in extracellular vesicles (EVs) isolated from induced human neuron, brain, cerebrospinal fluid, and plasma in comparison with the presumed NDEV markers NCAM1 and L1CAM by using super-resolution microscopy and biochemical assessments. Proteomic analysis of immunoprecipitated ATP1A3 brain-derived EVs shows higher enrichment of synaptic markers and cargo proteins relevant to Alzheimer's disease (AD) compared to NCAM1 or LICAM EVs. Single particle analysis shows the elevated amyloid-β positivity in ATP1A3 EVs from AD plasma, providing better diagnostic prediction of AD over other plasma biomarkers. Thus, ATP1A3 is a reliable target to isolate NDEV from biofluids for diagnostic research.
Source
You Y, Zhang Z, Sultana N, Ericsson M, Martens YA, Sun M, Kanekiyo T, Ikezu S, Shaffer SA, Ikezu T. ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids. Sci Adv. 2023 Sep 15;9(37):eadi3647. doi: 10.1126/sciadv.adi3647. Epub 2023 Sep 15. PMID: 37713494; PMCID: PMC10881047.