Targeting Neuroinflammation by Bioreactive Nanoparticles for Early Detection and Intervention of Alzheimer’s Disease
Bibliographic record
Abstract
Abstract Background Neuroinflammation plays a causal role in neurodegenerative Alzheimer’s disease (AD); it occurs long before clinical onset of AD. 1 Therefore, early detection of neuroinflammation is critical for early intervention before the irreversible neurodegeneration happens. To address this pressing need, our group has developed multifunctional bioreactive nanoparticles, consisting of blood‐brain barrier‐penetrating terpolymer and MnO 2 nanoparticles and conjugated anti‐Ab antibody (Ab‐TP‐MDNP). The system reduced oxidative stress and produced oxygen and paramagnetic Mn 2+ ions, thereby remodeling the brain microenvironment and enabling sensitive detection of early neuroinflammation prior to Ab plague formation in an APP transgenic TgCRND8+ AD mouse model. 2 We also demonstrated its effects on improving vascular functions, Ab elimination, energy metabolism, neuronal activity and cognitive function. 3‐4 Built on the foundation of previous findings, we investigate whether the TP‐MDNP is able enhance early detection of neuroinflammation regardless of Aß or tau expression and evaluate its therapeutic effect in AD mouse model of tauopathy. Method Three types of transgenic mouse model of AD, TgCRND8+, PS19 with tauopathy, and APP/PS1 were used in the MRI study. The diagnostic performance of Ab‐TP‐MDNP in MRI was also compared with PET imaging using F18‐florobetaben in TgCRND8+ mice. PS19 mice were treated with IV injection of TP‐MDNP for two weeks (2/week, 100 μmol Mn/kg b.w.) and the biomarkers for ROS, neuroinflammation, and p‐Tau expression were examined using immunohistochemistry and ELISA. Result Ab‐TP‐MDNP enhanced MRI signal significantly outperformed PET imaging by Ab‐targeted F18‐florobetaben in TgCRND8+ mice of 3 months and 6 months of age. Similar MRI imaging sensitivity was observed in PS19 and APP/PS1 mice with or without conjugated antibody against Ab or tau protein, suggesting the neuroinflammation activated MRI contrast enhancement as a common mechanism. In PS19, TP‐MDNP treatment significantly reduced total ROS, CA9 (a hypoxia marker) and p‐tau levels. Conclusion The results suggest that TP‐MDNP can enable MRI detection of neuroinflammation and reduce neurodegeneration pathogenetic factors such as ROS, hypoxia, and p‐tau in AD mouse brains. References 1. Zhang W, et al. Sig Transduct Target Ther 2023;8, 267. 2. He C, et al. Nano Today . 2020;35:100965. 3. Park E,. et al. Advanced Science . 2023 Apr;10(12):2207238. 4. Park E, et al. Biomaterials . 2025 Jan 24:123142.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".