ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids

Yang You; Zhengrong Zhang; Nadia Sultana; Maria Ericsson; Yuka A. Martens; Min Sun; Takahisa Kanekiyo; Seiko Ikezu; Scott A. Shaffer; Tsuneya Ikezu

doi:10.1126/sciadv.adi3647

ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids

Yang You, Zhengrong Zhang, Nadia Sultana, Maria Ericsson, Yuka A. Martens, Min Sun, Takahisa Kanekiyo, Seiko Ikezu, Scott A. Shaffer, Tsuneya Ikezu

Neuroscience

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	eadi3647
Journal	Science Advances
Volume	9
Issue number	37
DOIs	https://doi.org/10.1126/sciadv.adi3647
State	Published - 2023

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title = "ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids",

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{\textquoteright}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.",

author = "Yang You and Zhengrong Zhang and Nadia Sultana and Maria Ericsson and Martens, {Yuka A.} and Min Sun and Takahisa Kanekiyo and Seiko Ikezu and Shaffer, {Scott A.} and Tsuneya Ikezu",

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year = "2023",

doi = "10.1126/sciadv.adi3647",

language = "English (US)",

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T1 - ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids

AU - You, Yang

AU - Zhang, Zhengrong

AU - Sultana, Nadia

AU - Ericsson, Maria

AU - Martens, Yuka A.

AU - Sun, Min

AU - Kanekiyo, Takahisa

AU - Ikezu, Seiko

AU - Shaffer, Scott A.

AU - Ikezu, Tsuneya

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

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ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids

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