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However, noninvasive monitoring of tau protein secretion, a key biomarker of AD, across developmental stages, age\u2010related variations, and the interaction between apolipoprotein E (\n                    <jats:italic>APOE<\/jats:italic>\n                    ) and the tau protein axis is not yet accomplished. Here, the label\u2010free and non\u2010invasive detection of multiple tau variants dynamics across developmental stages, age\u2010related variants, and various\n                    <jats:italic>APOE<\/jats:italic>\n                    isogenic genotyes\u00a0is presented to investigate the\n                    <jats:italic>APOE<\/jats:italic>\n                    \u2013tau axis using human cerebral organoids (hCOs) combined with surface\u2010enhanced Raman spectroscopy (SERS). Principal component analysis (PCA) of SERS signals successfully identifies four developmental stages of hCOs: embryonic body, neuronal differentiation, maturation, and maintenance phases. Temporal dynamics of age\u2010related tau protein secretion are observed, reflecting characteristics associated with AD, which are diminished by astrocyte expression. PCA\u2010based dimensionality reduction of SERS signals further reveals distinct clustering for different\n                    <jats:italic>APOE<\/jats:italic>\n                    isogenic genotypes, with tau protein secretion increasing from\n                    <jats:italic>APOE2\/E2<\/jats:italic>\n                    to\n                    <jats:italic>APOE4\/E4<\/jats:italic>\n                    , providing direct insight into the\n                    <jats:italic>APOE<\/jats:italic>\n                    \u2013tau axis in AD. This study introduces a novel method for the non\u2010invasive clinical assessments of disease conditions, dynamics, and the relationship between\n                    <jats:italic>APOE<\/jats:italic>\n                    and tau in AD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202505660","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:36:19Z","timestamp":1748583379000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the\n                    <i>APOE<\/i>\n                    \u2013Tau Axis via Human Cerebral Organoids with Immuno\u2010SERS"],"prefix":"10.1002","volume":"12","author":[{"given":"Yongjae","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Biophysics Institute of Quantum Biophysics Sungkyunkwan University  Suwon 16419 Republic of 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Institute of Quantum Biophysics Sungkyunkwan University  Suwon 16419 Republic of Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence Sungkyunkwan University  Suwon 16419 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soomin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biophysics Institute of Quantum Biophysics Sungkyunkwan University  Suwon 16419 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences College of Medicine Seoul National University  Seoul 03080 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Won","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences College of Medicine Seoul National University  Seoul 03080 Republic of 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