MRI and Histological Analysis of Beta-Amyloid Plaques in Both Human Alzheimer's Disease and APP/PS1 Transgenic Mice

Purpose: To investigate the relationship between MR image contrast associated with beta-amlyloid (AP) plaques and their histology and compare the histopathological basis of image contrast and the relaxation mechanism associated with AP plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse tissues. Materials and Methods: With the aid of the previously developed histological coil, T-2*-weighted images and R-2* parametric maps were directly compared with histology stains acquired from the same set of Alzheimer's and APP/PS1 tissue slices. Results: The electron microscopy and histology images revealed significant differences in plaque morphology and associated iron concentration between AD and transgenic APP/PS1 mice tissue samples. For AD tissues, T-2* contrast of A beta-plaques was directly associated with the gradation of iron concentration. Plaques with significantly less iron load in the APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR images. Conclusion: These data suggest a duality in the relaxation mechanism where both high focal iron concentration and highly compact fibrillar beta-amyloid masses cause rapid proton transverse magnetization decay. For human tissues, the former mechanism is likely the dominant source of R-2* relaxation; for APP/PS1 animals, the latter is likely the major cause of increased transverse proton relaxation rate in A beta plaques. The data presented are essential for understanding the histopathological underpinning of MRI measurement associated with A beta plaques in humans and animals.