Molecular MRI of Neuroinflammation in Alzheimer's Disease using a Folate-targeted Nanoprobe

Alzheimer's disease (AD) is characterized by neuroinflammation driven by activated microglia, which plays a central role in the disease's progression. Non-invasive imaging techniques that can detect neuroinflammation are crucial for understanding disease mechanisms and evaluating potential treatments. The folate receptor (FR), particularly its beta isoform, has been identified as a marker of pro-inflammatory myeloid cells in other inflammatory diseases; however, its relationship with AD neuroinflammation has not been extensively studied.

This research aimed to investigate the expression of the folate receptor in microglia within mouse models of AD and to evaluate the use of molecular MRI (mMRI) for in vivo imaging of FR expression. To achieve this, researchers first measured FR expression in microglia using flow cytometry in APP/PS1 and P301S transgenic mouse models of AD.

They then prepared a folate-targeted nanoprobe for mMRI by functionalizing high T1-relaxivity liposomal gadolinium nanoparticles with folic acid. Following intravenous injection, the localization of this nanoprobe in the brains of aged transgenic and wild-type mice was assessed using T1-weighted MRI. Post-mortem microscopy was also conducted to measure the nanoprobe's localization relative to microglia and amyloid pathology.

The findings in both mouse models demonstrated that FR beta was significantly upregulated compared to wild-type mice (p < 0.05). This suggests that the folate receptor beta may be a viable target for imaging neuroinflammation in AD, potentially aiding in the development of new therapeutic strategies to target this inflammatory process.