Molecular MRI of Neuroinflammation in Alzheimer's Disease using a Folate-targeted Nanoprobe
- 1Texas Children's Hospital / Baylor College of Medicine
Abstract
Background: Neuroinflammation, driven by activated microglia, plays a central role in the pathogenesis of Alzheimer's disease (AD). Non-invasive imaging of neuroinflammation holds promise for advancing our understanding of disease mechanisms and evaluating anti-inflammatory therapeutic strategies. The folate receptor (FR), specifically its {beta} isoform, has been identified as a marker of pro-inflammatory myeloid cells in peripheral inflammatory diseases; however, its association with AD neuroinflammation remains unknown. In this work, we first determined FR expression in microglia in mouse models of AD and subsequently evaluated molecular MRI (mMRI) using a folate-targeted nanoprobe for in vivo imaging of the folate receptor expression. Methods and results: Microglial activation and FR expression in APP/PS1 and P301S transgenic mouse models of AD was measured using flow cytometry. A FR-targeted nanoprobe for mMRI was prepared by functionalizing high T1-relaxivity liposomal gadolinium nanoparticle with folic acid. Following intravenous injection, localization of the nanoprobe in the brains of aged transgenic and wild-type mice was measured using T1-weighted MRI. Post-mortem microscopy measured nanoprobe localization relative to microglia and amyloid pathology. In both mouse models, FR{beta} was significantly (p < 0.05) upregulated in pro-inflammatory microglia expressing TNF and IL-1{beta}. The folate-targeted nanoprobe demonstrated MR signal enhancement in the cortical and hippocampal regions of transgenic mice but not in wild type mice; non-targeted nanoprobe control did not demonstrate signal enhancement in brain of transgenic mice. Microscopy confirmed colocalization of FR-targeted nanoprobe with IBA1-positive microglia/macrophages and amyloid plaques. Conclusions: Pro-inflammatory microglia exhibit elevated levels of FR, and its measurement by non-invasive mMRI is a promising marker of neuroinflammation in AD.
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BibTeX
@misc{badachhape2026molecular,
title = {{Molecular MRI of Neuroinflammation in Alzheimer's Disease using a Folate-targeted Nanoprobe}},
author = {A. A. Badachhape and P. Bhandari and R. Khan and R. Bhavane and R. Menon and P. Parekh and P. Admane and E. Ngan and M. Srivastava and E. A. Tanifum and A. V. Annapragada and R. M. Ritzel and K. B. Ghaghada},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.761963},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.761963v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Molecular MRI of Neuroinflammation in Alzheimer's Disease using a Folate-targeted Nanoprobe
AU - A. A. Badachhape
AU - P. Bhandari
AU - R. Khan
AU - R. Bhavane
AU - R. Menon
AU - P. Parekh
AU - P. Admane
AU - E. Ngan
AU - M. Srivastava
AU - E. A. Tanifum
AU - A. V. Annapragada
AU - R. M. Ritzel
AU - K. B. Ghaghada
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.761963
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.761963v1
AB - Background: Neuroinflammation, driven by activated microglia, plays a central role in the pathogenesis of Alzheimer's disease (AD). Non-invasive imaging of neuroinflammation holds promise for advancing our understanding of disease mechanisms and evaluating anti-inflammatory therapeutic strategies. The folate receptor (FR), specifically its {beta} isoform, has been identified as a marker of pro-inflammatory myeloid cells in peripheral inflammatory diseases; however, its association with AD neuroinflammation remains unknown. In this work, we first determined FR expression in microglia in mouse models of AD and subsequently evaluated molecular MRI (mMRI) using a folate-targeted nanoprobe for in vivo imaging of the folate receptor expression. Methods and results: Microglial activation and FR expression in APP/PS1 and P301S transgenic mouse models of AD was measured using flow cytometry. A FR-targeted nanoprobe for mMRI was prepared by functionalizing high T1-relaxivity liposomal gadolinium nanoparticle with folic acid. Following intravenous injection, localization of the nanoprobe in the brains of aged transgenic and wild-type mice was measured using T1-weighted MRI. Post-mortem microscopy measured nanoprobe localization relative to microglia and amyloid pathology. In both mouse models, FR{beta} was significantly (p < 0.05) upregulated in pro-inflammatory microglia expressing TNF and IL-1{beta}. The folate-targeted nanoprobe demonstrated MR signal enhancement in the cortical and hippocampal regions of transgenic mice but not in wild type mice; non-targeted nanoprobe control did not demonstrate signal enhancement in brain of transgenic mice. Microscopy confirmed colocalization of FR-targeted nanoprobe with IBA1-positive microglia/macrophages and amyloid plaques. Conclusions: Pro-inflammatory microglia exhibit elevated levels of FR, and its measurement by non-invasive mMRI is a promising marker of neuroinflammation in AD.
ER -