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This galley proof is being listed electronically before publishing the final manuscript (It's not final version).

 
MicroRNA super-resolution imaging in blood for Alzheimer’s disease
Mirae Lee 1,2,3 (Ph.D.), Jiwon Woo 2,3 (Ph.D.), Sang Tae Kim4 (Ph.D.), Minho Moon5 (Ph.D.), Sang Yun Kim4 (M.D., Ph.D.), Hanna Cho6 (M.D., Ph.D.), Sujin Kim5 (Ph.D.), Han-Kyeol Kim6 (M.D., Ph.D.), Jeong-Yoon Park 1,2,3,* (M.D., Ph.D.)
1Department of Neurosurgery, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine,
2Department of Neurosurgery, The Spine and Spinal Cord Institute, Department of Neurosurgery, Gangnam Severance Hospital, Yonsei University College of Medicine,
3Department of Neurosurgery, Biomedical Research Center, Gangnam Severance Hospital, Yonsei University College of Medicine,
4Department of Neurology, Seoul National University Bundang Hospital,
5Department of Biochemistry, Konyang University College of Medicine,
6Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine
Abstract
We propose a novel blood biomarker detection method that uses miRNA super-resolution imaging to enable the early-diagnosis of Alzheimer’s-disease (AD). Here, we report a single-molecule detection method for visualizing disease-specific miRNA in tissue from an AD mice-model, and peripheral-blood mononuclear-cells (PBMCs) from AD-patients. Using optimized MAPs (Magnified Analysis of Proteome), we confirmed that five miRNAs contribute to neurodegenerative disease in the brain hippocampi of 5XFAD and wild-type mice. We also assessed PBMCs isolated from the whole-blood of AD-patients and a healthy control-group and subsequently used the miRNA super-resolution imaging to analyze those samples. We detected more miR-200a-3p expression in the cornu-ammonis-1 and dentate-gyrus regions of 3-month-old 5XFAD mice than wild-type mice. Additionally, miRNA super-resolution imaging of blood provides AD diagnosis platform for studying miRNA regulation inside cells at the single-molecule level. Our results present a potential liquid biopsy method that could improve the diagnosis of early-stage AD and other diseases.
Abstract, Accepted Manuscript(in press) [Submitted on September 26, 2022, Accepted on November 16, 2022]
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