Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the APOE-Tau Axis via Human Cerebral Organoids with Immuno-SERS
Summary
Noninvasive monitoring of Alzheimer's disease (AD) biomarkers is essential for early diagnosis and treatment efficacy. However, noninvasive monitoring of tau protein secretion, a key biomarker of AD, across developmental stages, age-related variations, and the interaction between apolipoprotein E (APOE) and the tau protein axis is not yet accomplished. Here, the label-free and non-invasive detection of multiple tau variants dynamics across developmental stages, age-related variants, and various APOE isogenic genotyes is presented to investigate the APOE-tau axis using human cerebral organoids (hCOs) combined with surface-enhanced 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-related tau protein secretion are observed, reflecting characteristics associated with AD, which are diminished by astrocyte expression. PCA-based dimensionality reduction of SERS signals further reveals distinct clustering for different APOE isogenic genotypes, with tau protein secretion increasing from APOE2/E2 to APOE4/E4, providing direct insight into the APOE-tau axis in AD. This study introduces a novel method for the non-invasive clinical assessments of disease conditions, dynamics, and the relationship between APOE and tau in AD. © 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.
| Authors | Jo Y, Kim Y, Kang R, Lee S, Nguyen DD, Park S, Lee D, Han JW, Mook-Jung I, Lee LP, Park JC, Kim I |
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| Journal | Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
| Publication Date | 2025 Sep;12(35):e05660 |
| PubMed | 40444455 |
| PubMed Central | PMC12463057 |
| DOI | 10.1002/advs.202505660 |