Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration
TL;DR
dMRI captures plaque‐associated cellular pathology and supports biologically informed interpretation of imaging contrasts in AD.
Abstract
Abstract INTRODUCTION Amyloid plaque deposition is a defining feature of Alzheimer's disease (AD), yet how plaque‐associated cellular alterations are reflected in noninvasive imaging remains unclear.
Methods
We integrated high‐resolution diffusion magnetic resonance imaging (dMRI) with spatial transcriptomics (ST) in an AD mouse model. Spatial correlations were assessed across the whole brain and in disease–control and plaque–non‐plaque comparisons. Neural network models were trained to predict AD‐associated cell types from dMRI metrics.
Results
dMRI metrics showed moderate spatial correlations (r = −0.41 to 0.36) with oligodendrocyte‐ and neuron‐related gene expression. Disease–control comparisons revealed region‐specific MRI‐derived microstructural alterations aligned with transcriptional changes in microglia, astrocytes, oligodendrocytes, and neurons. Plaque‐rich regions exhibited distinct diffusion and susceptibility signatures associated with oligodendrocyte and microglial expression. Neural networks predicted spatial distributions of AD‐associated cell types with 80%–86% accuracy.
Discussion
dMRI captures plaque‐associated cellular pathology and supports biologically informed interpretation of imaging contrasts in AD.