{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:08:36Z","timestamp":1790060916060,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81827901"],"award-info":[{"award-number":["81827901"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U25A20562"],"award-info":[{"award-number":["U25A20562"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mitochondrial dysfunction is one of the earliest pathological features of Alzheimer's disease (AD), preceding overt neurodegeneration and cognitive decline. Amyloid\u2010\u03b2 (A\u03b2) accumulation has long been considered a central pathogenic event in AD, yet how A\u03b2 toxicity is mechanistically linked to mitochondrial impairment during early disease stages remains incompletely understood. To address this, we combined multi\u2010omics with in vivo and in vitro genetic interventions. Here, we show that malic enzyme 3 (Me3) links A\u03b2 aggregation to mitochondrial dysfunction in APP\/PS1 mice and neuronal cells. At ultra\u2010early and early AD stages (3 and 6 months), Me3 was upregulated and accumulated within mitochondria, where it colocalized with A\u03b242 and physically interacted with it, an association linked to oxidative stress and impaired mitophagy. Knockdown of Me3 reduced mitochondrial reactive oxygen species, improved mitochondrial morphology, and alleviated mitophagy defects in both cellular and mouse models, with statistical significance across these functional measurements (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). These results suggest that Me3 functions not only as a metabolic responder to A\u03b2\u2010associated stress but also as a contributor to early mitochondrial pathology. By identifying the A\u03b2\u2010Me3 axis, this study provides mechanistic insight into early mitochondrial dysfunction in AD, while further validation in human AD samples remains necessary.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70984","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:52:01Z","timestamp":1788857521000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics Analysis Reveals That A\u03b242\u2010 Me3 Co\u2010Aggregation Induces Mitophagy Blockade in Early Stages of Alzheimer's Disease"],"prefix":"10.1002","volume":"7","author":[{"given":"Wenjie","family":"Zhu","sequence":"first","affiliation":[{"name":"The Key Laboratory for Biomedical Photonics of MOE At Wuhan National Laboratory for Optoelectronics\u2010Hubei Bioinformatics and Molecular Imaging Key Laboratory Systems Biology Theme Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Biomedical Photonics of MOE At Wuhan National Laboratory for Optoelectronics\u2010Hubei Bioinformatics and Molecular Imaging Key Laboratory Systems Biology Theme Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengjie","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Biomedical Photonics of MOE At Wuhan National Laboratory for Optoelectronics\u2010Hubei Bioinformatics and Molecular Imaging Key Laboratory Systems Biology Theme Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhong","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Biomedical Photonics of MOE At Wuhan National Laboratory for Optoelectronics\u2010Hubei Bioinformatics and Molecular Imaging Key Laboratory Systems Biology Theme Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Life Sciences Wuhan University of Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Biomedical Photonics of MOE At Wuhan National Laboratory for Optoelectronics\u2010Hubei Bioinformatics and Molecular Imaging Key Laboratory Systems Biology Theme Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","unstructured":"\u201c2022 Alzheimer's Disease Facts and Figures \u201dAlzheimer's & Dementia18 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